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Maciej Siedlar - One of the best experts on this subject based on the ideXlab platform.

  • reprint of alterations of trim21 mrna expression during monocyte maturation
    Immunobiology, 2017
    Co-Authors: Marzena Lenart, Rafal Szatanek, Kazimierz Weglarczyk, Malgorzata Stec, Karolina Bukowskastrakova, Jaroslaw Czyz, Magdalena Rutkowskazapala, Anna Gruca, Maciej Siedlar
    Abstract:

    Abstract Tripartite motif-containing protein 21 (TRIM21) play a dual role in the cytoplasm of the cells where it facilitates destruction of some antibody-coated viruses and some bacteria, and initiates synthesis of proinflammatory cytokines. Macrophages and CD16+ monocyte subset can particularly participate in a proinflammatory response caused by viral infection, however, the molecular mechanisms underlying these processes are not fully understood. The aim of this study was to determine the level of TRIM21-mRNA expression in monocyte subsets including: classical (CD14++CD16−), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) monocytes, as well as during in vitro differentiation of the isolated monocytes towards dendritic cells or macrophages. Our results revealed that the level of TRIM21 mRNA expression was significantly lower in CD16- monocytes, when compared to CD16+ cells and the whole monocyte population, yet no significant differences were observed when CD16+ population was divided into intermediate and non-classical subsets. More pronounced differences were observed in the case of monocyte-derived macrophages (MDM) and dendritic cells (DCs). TRIM21-mRNA expression level was app. 6-fold higher in DCs, and app. 16-fold higher in MDM (p  Our results may suggest the new mechanism of increased proinflammatory cytokine production by CD16+ (intermediate and non-classical) monocytes and macrophages, at least in patients with acute or chronic infections, caused by enveloped viruses. We suggest that TRIM21 may be one of the factors associated with the “switching on” the proinflammatory programme in CD16+ monocytes or monocyte-derived macrophages.

  • alterations of trim21 mrna expression during monocyte maturation
    Immunobiology, 2017
    Co-Authors: Marzena Lenart, Rafal Szatanek, Kazimierz Weglarczyk, Malgorzata Stec, Karolina Bukowskastrakova, Jaroslaw Czyz, Magdalena Rutkowskazapala, Anna Gruca, Maciej Siedlar
    Abstract:

    Tripartite motif-containing protein 21 (TRIM21) play a dual role in the cytoplasm of the cells where it facilitates destruction of some antibody-coated viruses and some bacteria, and initiates synthesis of proinflammatory cytokines. Macrophages and CD16+ monocyte subset can particularly participate in a proinflammatory response caused by viral infection, however, the molecular mechanisms underlying these processes are not fully understood. The aim of this study was to determine the level of TRIM21-mRNA expression in monocyte subsets including: classical (CD14++CD16−), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) monocytes, as well as during in vitro differentiation of the isolated monocytes towards dendritic cells or macrophages. Our results revealed that the level of TRIM21 mRNA expression was significantly lower in CD16- monocytes, when compared to CD16+ cells and the whole monocyte population, yet no significant differences were observed when CD16+ population was divided into intermediate and non-classical subsets. More pronounced differences were observed in the case of monocyte-derived macrophages (MDM) and dendritic cells (DCs). TRIM21-mRNA expression level was app. 6-fold higher in DCs, and app. 16-fold higher in MDM (p < 0,01), when compared to freshly isolated monocytes. Our results may suggest the new mechanism of increased proinflammatory cytokine production by CD16+ (intermediate and non-classical) monocytes and macrophages, at least in patients with acute or chronic infections, caused by enveloped viruses. We suggest that TRIM21 may be one of the factors associated with the “switching on” the proinflammatory programme in CD16+ monocytes or monocyte-derived macrophages.

  • preparations of intravenous immunoglobulins diminish the number and proinflammatory response of cd14 CD16 monocytes in common variable immunodeficiency cvid patients
    Clinical Immunology, 2011
    Co-Authors: Maciej Siedlar, Kazimierz Weglarczyk, Karolina Bukowskastrakova, Marzena Lenart, Anna Szaflarska, Monika Bajkrzyworzeka, Magdalena Strach, Magdalena Rutkowska, Anna Pituchnoworolska, Danuta Kowalczyk
    Abstract:

    Abstract We have studied the effect of intravenous immunoglobulins (IVIG) on monocyte subpopulations and cytokine production in patients with CVID. The absolute number of CD14+CD16++ monocytes decreased on average 2.5-fold 4 h after IVIG and after 20 h returned to the baseline. The cytokine level in the supernatants of peripheral blood mononuclear cells (PBMC) after ex vivo LPS stimulation demonstrated the > 2-fold decrease in TNF production 4 h after IVIG. The TNF expression, which is higher in the CD14+CD16++ monocytes, was decreased in these cells by IVIG in 4/7 CVID cases. In vitro exposure of the healthy individuals' monocytes to the IVIG preparation resulted in reduced TNF production, which was overcome by blockade of the FcγRIIB in the CD14+CD16++ CD32Bhigh monocytes. Our data suggest that reduction in the number of CD14+CD16++ monocytes and the blockade of their cytokine production via triggering CD32B can contribute to the anti-inflammatory action of IVIG.

  • antitumor response of cd14 CD16 monocyte subpopulation
    Experimental Hematology, 2004
    Co-Authors: Anna Szaflarska, Kazimierz Weglarczyk, Maciej Siedlar, Monika Bajkrzyworzeka, Irena Ruggiero, Barbara Hajto, Marek Zembala
    Abstract:

    Objective Two main subpopulations of human blood monocytes are distinguished on the basis of CD14 and CD16 expression: the major population with enhanced expression of CD14 (CD14 ++ monocytes) and the minor one with a weak expression of CD14 coexpressing CD16 (CD14 + /CD16 + monocytes). As monocytes and macrophages are involved in antitumor response of the host, we assessed the ability of CD14 + /CD16 + monocytes to produce cytokines (intracellular expression, release) and reactive oxygen and nitrogen (ROI, RNI) intermediates following stimulation in vitro with tumor cells. Materials and methods Monocytes were isolated by elutriation and their subpopulations by FACS sorting. Monocytes and their subpopulations were cocultured with tumor cells. Cytokine (TNF-α, IL-12, and IL-10) production was assessed by determination of intracellular protein expression by flow cytometry, and release by ELISA. ROI induction was detected by chemiluminescence and O 2 − production by flow cytometry, whereas RNI by intracellular expression of inducible NO synthase (iNOS) and nitric oxide (NO) release assessed colorimetrically. Results CD14 + /CD16 + monocytes stimulated with tumor cells showed significantly enhanced production of TNF-α, IL-12p40, IL-12p70 (intracellular expression, release), whereas little IL-10 release was observed. CD14 + /CD16 + subpopulation did not produce ROI, but showed an increased iNOS expression and NO release. CD14 + /CD16 + monocytes also exhibited enhanced cytotoxic and cytostatic activities against tumor cells. Conclusions CD14 + /CD16 + cells constitute the main subpopulation of blood monocytes involved in antitumor response as judged by enhanced production of proinflammatory cytokines, RNI, and increased cytotoxic/cytostatic activity.

  • the proinflammatory cd14 CD16 dr monocytes are a major source of tnf
    Journal of Immunology, 2002
    Co-Authors: Kaiuwe Belge, Maciej Siedlar, Marion Frankenberger, Farshid Dayyani, Alexia Horelt, Bernhard Frankenberger, Terje Espevik, Loms Zieglerheitbrock
    Abstract:

    In human blood two monocyte populations can be distinguished, i.e., the CD14(++)CD16(-)DR(+) classical monocytes and the CD14(+)CD16(+)DR(++) proinflammatory monocytes that account for only 10% of all monocytes. We have studied TNF production in these two types of cells using three-color immunofluorescence and flow cytometry on whole peripheral blood samples stimulated with either LPS or with the bacterial lipopeptide S-(2,3-bis(palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys(4)-OH,trihydrochloride (Pam3Cys). After stimulation with LPS the median fluorescence intensity for TNF protein was 3-fold higher in the proinflammatory monocytes when compared with the classical monocytes. After stimulation with Pam3Cys they almost exclusively responded showing 10-fold-higher levels of median fluorescence intensity for TNF protein. The median fluorescence intensity for Toll-like receptor 2 cell surface protein was found 2-fold higher on CD14(+)CD16(+)DR(++) monocytes, which may explain, in part, the higher Pam3Cys-induced TNF production by these cells. When analyzing secretion of TNF protein into the supernatant in PBMCs after depletion of CD16(+) monocytes we found a reduction of LPS-induced TNF by 28% but Pam3Cys-induced TNF was reduced by 64%. This indicates that the minor population of CD14(+)CD16(+) monocytes are major producers of TNF in human blood.

Toshio Imanishi - One of the best experts on this subject based on the ideXlab platform.

  • acute phase glucose fluctuation is negatively correlated with myocardial salvage after acute myocardial infarction
    Circulation, 2014
    Co-Authors: Ikuko Teraguchi, Yuichi Ozaki, Toshio Imanishi, Yasutsugu Shiono, Takashi Tanimoto, Kohei Ishibashi, Minoru Ueyama, Makoto Orii, Kunihiro Shimamura, Takashi Yamano
    Abstract:

    BACKGROUND It remains unclear whether glycemic fluctuation immediately after acute myocardial infarction (AMI) can affect myocardial damage. This study investigated the impact of glucose fluctuation on myocardial salvage following successful recanalization of primary AMI. METHODS AND RESULTS A total of 36 consecutive patients with AMI were studied. Glycemic variability, as indicated by the mean amplitude of glycemic excursion (MAGE), was measured on a continuous glucose monitoring system. Three subsets (CD14(+)CD16(-), CD14(++)CD16(+) and CD14(+-)CD16(+)) were measured on flow cytometry 1, 2, 3, 4 and 5 days after AMI onset. A 2-h oral glucose test was performed in 23 patients who had no previous diagnosis of diabetes and/or glycated hemoglobin <6.5%, after the onset of AMI at 2 weeks. Plasma active glucagon-like peptide (GLP)-1 level was measured in each sample. The extent of myocardial salvage 7 days after AMI was evaluated on cardiovascular magnetic resonance imaging. MAGE and the peak CD14(+)CD16(-) monocyte level were significantly negatively correlated with myocardial salvage index (MSI). MAGE was significantly correlated with peak CD14(+)CD16(-) monocyte level. Of interest, plasma GLP-1 level was significantly positively correlated with MSI and significantly negatively correlated with MAGE. CONCLUSIONS Glucose fluctuations during the acute phase of AMI affect MSI, indicating that manipulation of glucose variability from peak to nadir might be a potential therapeutic target for salvaging ischemic damage.

  • circulating cd14 CD16 monocyte subsets as biomarkers of the severity of coronary artery disease in patients with stable angina pectoris
    Circulation, 2012
    Co-Authors: Yuichi Ozaki, Toshio Imanishi, Akira Taruya, Hiroshi Aoki, Tomizo Masuno, Yasutsugu Shiono, Kenichi Komukai, Takashi Tanimoto, Hironori Kitabata, Takashi Akasaka
    Abstract:

    BACKGROUND Circulating monocytes can be divided into 2 subsets typically identified by the expression of CD14 and CD16. Although previous studies have shown that circulating monocytes contribute to the progression of coronary atherosclerotic lesions, the relationship between the severity of coronary artery disease (CAD) and the 2 distinct monocyte subsets has not previously been evaluated. We investigated the relationship between the monocyte subsets and the severity of CAD assessed by coronary angiography (CAG) in patients with stable angina pectoris (SAP). METHODS AND RESULTS  We enrolled 125 patients who underwent diagnostic CAG. Patients were divided into 3 groups: those without CAD, those with single-vessel disease (SVD), and those with multiple-vessel disease (MVD). In addition, the severity of CAD was evaluated by Gensini score. The 2 monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were measured by flow cytometry. Circulating CD14(+)CD16(+) monocytes were more frequently observed in patients with MVD than in those with SVD or without CAD. The proportion of CD14(+)CD16(+) monocytes positively correlated with Gensini score (r=0.618, P<0.001). Multivariate logistic regression analysis revealed that the proportion of CD14(+)CD16(+) monocytes was an independent contributor to MVD (odds ratio: 1.475; 95% confidence interval: 1.273-1.708, P<0.001). CONCLUSIONS  A preferential increase in peripheral CD14(+)CD16(+) monocytes may be closely related to the severity of CAD in patients with SAP.

  • association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pectoris
    Atherosclerosis, 2010
    Co-Authors: Toshio Imanishi, Kenichi Komukai, Takashi Tanimoto, Hiroto Tsujioka, Hideyuki Ikejima, Akio Kuroi, Kohei Ishibashi, Yasushi Ino, Tatsuya Takeshita, Takashi Akasaka
    Abstract:

    Abstract Objectives We examined whether distinct monocyte subsets relate in specific ways to coronary fibrous cap thickness (FCT) in patients with unstable angina pectoris (UAP). Methods Forty patients with UAP who underwent percutaneous coronary intervention were enrolled in this study. The changes in the non-culprit FCT were assessed by optical coherence tomography (OCT) at baseline and after 9 months. The distinct monocyte subsets (CD14 + CD16 − CCR2 + and CD14 + CD16 + CX3CR1 + ) were measured by flow cytometry. Results The percent change in FCT showed significantly negative correlation with the percent changes in CD14 + CD16 + CX3CR1 + monocytes, but not CD14 + CD16 − CCR2 + monocytes. In addition, the percent change in CD14 + CD16 + CX3CR1 + monocytes was significantly decreased in the group of patients who received statin treatment compared with the group of patients who did not. Of interest, there was a close relationship between CD14 + CD16 + CX3CR1 + monocytes and levels of C-reactive protein, but not lipid profiles, including low-density lipoprotein cholesterol and low-/high-density lipoprotein cholesterol ratio. Conclusions CD14 + CD16 + CX3CR1 + monocytes may have a role in coronary plaque vulnerability.

  • association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64 slice multidetector computed tomography in patients with stable angina pectoris
    Atherosclerosis, 2010
    Co-Authors: Manabu Kashiwagi, Yuichi Ozaki, Toshio Imanishi, Kenichi Komukai, Takashi Tanimoto, Hiroto Tsujioka, Hideyuki Ikejima, Akio Kuroi, Kohei Ishibashi, Yasushi Ino
    Abstract:

    Abstract Objective The aim of the present study was to examine the relation between monocyte subsets and the presence, extent, and vulnerability characteristics of non-calcified coronary plaques (NCPs) as assessed by multidetector computed tomography (MDCT). Methods We studied 73 patients with stable angina pectoris who underwent MDCT. Two monocyte subsets (CD14 + CD16 − and CD14 + CD16 + ) were measured by flow cytometry. Coronary artery plaques were assessed by 64-slice MDCT. We defined NCP vulnerability according to the presence of positive remodeling (remodeling index > 1.05) and/or low CT attenuation plaques ( Results A total of 40 (55%) patients had identifiable vulnerable plaques. The relative proportion of CD14 + CD16 + monocytes was significantly greater in patients with 1 or multiple vulnerable plaques than in patients with no vulnerable plaques or control (healthy) subjects. In addition, the relative proportion of CD14 + CD16 + monocytes was positively correlated with remodeling index ( r  = 0.40, P r  = −0.34, P Conclusion The present results suggest that an increased subset of CD14 + CD16 + monocytes is related to coronary plaque vulnerability in patients with stable angina pectoris.

  • impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction
    Journal of the American College of Cardiology, 2009
    Co-Authors: Hiroto Tsujioka, Toshio Imanishi, Takashi Tanimoto, Hironori Kitabata, Hideyuki Ikejima, Akio Kuroi, Shigeho Takarada, Keishi Okochi, Yu Arita, Kohei Ishibashi
    Abstract:

    Objectives We examined whether distinct monocyte subsets contribute in specific ways to myocardial salvage in patients with acute myocardial infarction (AMI). Background Recent studies have shown that monocytes in human peripheral blood are heterogeneous. Methods We studied 36 patients with primary AMI. Peripheral blood sampling was performed 1, 2, 3, 4, 5, 8, and 12 days after AMI onset. Two monocyte subsets (CD14+CD16−and CD14+CD16+) were measured by flow cytometry. The extent of myocardial salvage 7 days after AMI was evaluated by cardiovascular magnetic resonance imaging as the difference between myocardium at risk (T2-weighted hyperintense lesion) and myocardial necrosis (delayed gadolinium enhancement). Cardiovascular magnetic resonance imaging was also performed 6 months after AMI. Results Circulating CD14+CD16−and CD14+CD16+monocytes increased in AMI patients, peaking on days 3 and 5 after onset, respectively. Importantly, the peak levels of CD14+CD16−monocytes, but not those of CD14+CD16+monocytes, were significantly negatively associated with the extent of myocardial salvage. We also found that the peak levels of CD14+CD16−monocytes, but not those of CD14+CD16+monocytes, were negatively correlated with recovery of left ventricular ejection fraction 6 months after infarction. Conclusions The peak levels of CD14+CD16−monocytes affect both the extent of myocardial salvage and the recovery of left ventricular function after AMI, indicating that the manipulation of monocyte heterogeneity could be a novel therapeutic target for salvaging ischemic damage.

Takashi Tanimoto - One of the best experts on this subject based on the ideXlab platform.

  • acute phase glucose fluctuation is negatively correlated with myocardial salvage after acute myocardial infarction
    Circulation, 2014
    Co-Authors: Ikuko Teraguchi, Yuichi Ozaki, Toshio Imanishi, Yasutsugu Shiono, Takashi Tanimoto, Kohei Ishibashi, Minoru Ueyama, Makoto Orii, Kunihiro Shimamura, Takashi Yamano
    Abstract:

    BACKGROUND It remains unclear whether glycemic fluctuation immediately after acute myocardial infarction (AMI) can affect myocardial damage. This study investigated the impact of glucose fluctuation on myocardial salvage following successful recanalization of primary AMI. METHODS AND RESULTS A total of 36 consecutive patients with AMI were studied. Glycemic variability, as indicated by the mean amplitude of glycemic excursion (MAGE), was measured on a continuous glucose monitoring system. Three subsets (CD14(+)CD16(-), CD14(++)CD16(+) and CD14(+-)CD16(+)) were measured on flow cytometry 1, 2, 3, 4 and 5 days after AMI onset. A 2-h oral glucose test was performed in 23 patients who had no previous diagnosis of diabetes and/or glycated hemoglobin <6.5%, after the onset of AMI at 2 weeks. Plasma active glucagon-like peptide (GLP)-1 level was measured in each sample. The extent of myocardial salvage 7 days after AMI was evaluated on cardiovascular magnetic resonance imaging. MAGE and the peak CD14(+)CD16(-) monocyte level were significantly negatively correlated with myocardial salvage index (MSI). MAGE was significantly correlated with peak CD14(+)CD16(-) monocyte level. Of interest, plasma GLP-1 level was significantly positively correlated with MSI and significantly negatively correlated with MAGE. CONCLUSIONS Glucose fluctuations during the acute phase of AMI affect MSI, indicating that manipulation of glucose variability from peak to nadir might be a potential therapeutic target for salvaging ischemic damage.

  • circulating cd14 CD16 monocyte subsets as biomarkers of the severity of coronary artery disease in patients with stable angina pectoris
    Circulation, 2012
    Co-Authors: Yuichi Ozaki, Toshio Imanishi, Akira Taruya, Hiroshi Aoki, Tomizo Masuno, Yasutsugu Shiono, Kenichi Komukai, Takashi Tanimoto, Hironori Kitabata, Takashi Akasaka
    Abstract:

    BACKGROUND Circulating monocytes can be divided into 2 subsets typically identified by the expression of CD14 and CD16. Although previous studies have shown that circulating monocytes contribute to the progression of coronary atherosclerotic lesions, the relationship between the severity of coronary artery disease (CAD) and the 2 distinct monocyte subsets has not previously been evaluated. We investigated the relationship between the monocyte subsets and the severity of CAD assessed by coronary angiography (CAG) in patients with stable angina pectoris (SAP). METHODS AND RESULTS  We enrolled 125 patients who underwent diagnostic CAG. Patients were divided into 3 groups: those without CAD, those with single-vessel disease (SVD), and those with multiple-vessel disease (MVD). In addition, the severity of CAD was evaluated by Gensini score. The 2 monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were measured by flow cytometry. Circulating CD14(+)CD16(+) monocytes were more frequently observed in patients with MVD than in those with SVD or without CAD. The proportion of CD14(+)CD16(+) monocytes positively correlated with Gensini score (r=0.618, P<0.001). Multivariate logistic regression analysis revealed that the proportion of CD14(+)CD16(+) monocytes was an independent contributor to MVD (odds ratio: 1.475; 95% confidence interval: 1.273-1.708, P<0.001). CONCLUSIONS  A preferential increase in peripheral CD14(+)CD16(+) monocytes may be closely related to the severity of CAD in patients with SAP.

  • association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pectoris
    Atherosclerosis, 2010
    Co-Authors: Toshio Imanishi, Kenichi Komukai, Takashi Tanimoto, Hiroto Tsujioka, Hideyuki Ikejima, Akio Kuroi, Kohei Ishibashi, Yasushi Ino, Tatsuya Takeshita, Takashi Akasaka
    Abstract:

    Abstract Objectives We examined whether distinct monocyte subsets relate in specific ways to coronary fibrous cap thickness (FCT) in patients with unstable angina pectoris (UAP). Methods Forty patients with UAP who underwent percutaneous coronary intervention were enrolled in this study. The changes in the non-culprit FCT were assessed by optical coherence tomography (OCT) at baseline and after 9 months. The distinct monocyte subsets (CD14 + CD16 − CCR2 + and CD14 + CD16 + CX3CR1 + ) were measured by flow cytometry. Results The percent change in FCT showed significantly negative correlation with the percent changes in CD14 + CD16 + CX3CR1 + monocytes, but not CD14 + CD16 − CCR2 + monocytes. In addition, the percent change in CD14 + CD16 + CX3CR1 + monocytes was significantly decreased in the group of patients who received statin treatment compared with the group of patients who did not. Of interest, there was a close relationship between CD14 + CD16 + CX3CR1 + monocytes and levels of C-reactive protein, but not lipid profiles, including low-density lipoprotein cholesterol and low-/high-density lipoprotein cholesterol ratio. Conclusions CD14 + CD16 + CX3CR1 + monocytes may have a role in coronary plaque vulnerability.

  • association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64 slice multidetector computed tomography in patients with stable angina pectoris
    Atherosclerosis, 2010
    Co-Authors: Manabu Kashiwagi, Yuichi Ozaki, Toshio Imanishi, Kenichi Komukai, Takashi Tanimoto, Hiroto Tsujioka, Hideyuki Ikejima, Akio Kuroi, Kohei Ishibashi, Yasushi Ino
    Abstract:

    Abstract Objective The aim of the present study was to examine the relation between monocyte subsets and the presence, extent, and vulnerability characteristics of non-calcified coronary plaques (NCPs) as assessed by multidetector computed tomography (MDCT). Methods We studied 73 patients with stable angina pectoris who underwent MDCT. Two monocyte subsets (CD14 + CD16 − and CD14 + CD16 + ) were measured by flow cytometry. Coronary artery plaques were assessed by 64-slice MDCT. We defined NCP vulnerability according to the presence of positive remodeling (remodeling index > 1.05) and/or low CT attenuation plaques ( Results A total of 40 (55%) patients had identifiable vulnerable plaques. The relative proportion of CD14 + CD16 + monocytes was significantly greater in patients with 1 or multiple vulnerable plaques than in patients with no vulnerable plaques or control (healthy) subjects. In addition, the relative proportion of CD14 + CD16 + monocytes was positively correlated with remodeling index ( r  = 0.40, P r  = −0.34, P Conclusion The present results suggest that an increased subset of CD14 + CD16 + monocytes is related to coronary plaque vulnerability in patients with stable angina pectoris.

  • impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction
    Journal of the American College of Cardiology, 2009
    Co-Authors: Hiroto Tsujioka, Toshio Imanishi, Takashi Tanimoto, Hironori Kitabata, Hideyuki Ikejima, Akio Kuroi, Shigeho Takarada, Keishi Okochi, Yu Arita, Kohei Ishibashi
    Abstract:

    Objectives We examined whether distinct monocyte subsets contribute in specific ways to myocardial salvage in patients with acute myocardial infarction (AMI). Background Recent studies have shown that monocytes in human peripheral blood are heterogeneous. Methods We studied 36 patients with primary AMI. Peripheral blood sampling was performed 1, 2, 3, 4, 5, 8, and 12 days after AMI onset. Two monocyte subsets (CD14+CD16−and CD14+CD16+) were measured by flow cytometry. The extent of myocardial salvage 7 days after AMI was evaluated by cardiovascular magnetic resonance imaging as the difference between myocardium at risk (T2-weighted hyperintense lesion) and myocardial necrosis (delayed gadolinium enhancement). Cardiovascular magnetic resonance imaging was also performed 6 months after AMI. Results Circulating CD14+CD16−and CD14+CD16+monocytes increased in AMI patients, peaking on days 3 and 5 after onset, respectively. Importantly, the peak levels of CD14+CD16−monocytes, but not those of CD14+CD16+monocytes, were significantly negatively associated with the extent of myocardial salvage. We also found that the peak levels of CD14+CD16−monocytes, but not those of CD14+CD16+monocytes, were negatively correlated with recovery of left ventricular ejection fraction 6 months after infarction. Conclusions The peak levels of CD14+CD16−monocytes affect both the extent of myocardial salvage and the recovery of left ventricular function after AMI, indicating that the manipulation of monocyte heterogeneity could be a novel therapeutic target for salvaging ischemic damage.

Gunnar H. Heine - One of the best experts on this subject based on the ideXlab platform.

  • supersage evidence for cd14 CD16 monocytes as a third monocyte subset
    Blood, 2011
    Co-Authors: Adam M. Zawada, Kyrill S. Rogacev, Danilo Fliser, Bjorn Rotter, Peter Winter, Rolfr Marell, Gunnar H. Heine
    Abstract:

    Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14++CD16−, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. Current knowledge on human monocyte heterogeneity is still incomplete: while it is increasingly acknowledged that CD14++CD16+ monocytes are of outstanding significance in 2 global health issues, namely HIV-1 infection and atherosclerosis, CD14++CD16+ monocytes remain the most poorly characterized subset so far. We therefore developed a method to purify the 3 monocyte subsets from human blood and analyzed their transcriptomes using SuperSAGE in combination with high-throughput sequencing. Analysis of 5 487 603 tags revealed unique identifiers of CD14++CD16+ monocytes, delineating these cells from the 2 other monocyte subsets. Gene Ontology (GO) enrichment analysis suggests diverse immunologic functions, linking CD14++CD16+ monocytes to Ag processing and presentation (eg, CD74 , HLA-DR , IFI30 , CTSB ), to inflammation and monocyte activation (eg, TGFB1 , AIF1 , PTPN6 ), and to angiogenesis (eg, TIE2 , CD105 ). In conclusion, we provide genetic evidence for a distinct role of CD14++CD16+ monocytes in human immunity. After CD14++CD16+ monocytes have earlier been discussed as a potential therapeutic target in inflammatory diseases, we are hopeful that our data will spur further research in the field of monocyte heterogeneity.

  • cd14 CD16 monocytes and cardiovascular outcome in patients with chronic kidney disease
    European Heart Journal, 2011
    Co-Authors: Kyrill S. Rogacev, Adam M. Zawada, Danilo Fliser, C Ulrich, Sarah Seiler, Birgit Reichart, Esther Herath, Daniel Roth, Gunnar H. Heine
    Abstract:

    Aims Patients with chronic kidney disease (CKD) pose a worldwide growing burden to health care systems due to accelerated atherosclerosis and subsequent high cardiovascular (CV) morbidity. Atherogenesis is prominently driven by monocytes and monocyte-derived macrophages. The expression of CD14 and CD16 characterizes three monocyte subsets: CD14++CD16−, CD14++CD16+, and CD14(+)CD16+ cells; the latter two are often denoted as ‘proinflammatory’ CD16+ monocytes. Despite an association between CD16+ monocyte counts and higher CV risk in cross-sectional cohorts, the prognostic impact of elevated CD16+ monocyte counts is poorly understood. Methods and results We assessed monocyte heterogeneity using flow cytometry in 119 patients with non-dialysis CKD, who were prospectively followed for a median of 4.9 (inter-quartile range 4.8–5.0) years for the occurrence of CV events. In addition, we assessed expression of chemokine receptors on monocyte subsets. CD14++CD16+ monocyte were independently associated with CV events [hazard ratio (for an increase of 10 cells/μL) 1.26 (confidence interval: 1.04–1.52; P = 0.018)] after adjustment for variables that significantly affected CD14++CD16+ cell counts at baseline. Across the spectrum of CKD, CD14++CD16+ monocytes selectively expressed CCR5. Conclusion We found that CD14++CD16+ monocytes were independently associated with CV events in non-dialysis CKD patients. Our results support the notion that CD16+ monocytes rather than CD16− monocytes are involved in human atherosclerosis.

  • haemodialysis induced transient CD16 monocytopenia and cardiovascular outcome
    Nephrology Dialysis Transplantation, 2009
    Co-Authors: Kyrill S. Rogacev, Danilo Fliser, Maren Ziegelin, C Ulrich, Sarah Seiler, Matthias Girndt, Gunnar H. Heine
    Abstract:

    Background. Haemodialysis with bioincompatible membranes led to transient leukocyte activation and intra-dialytic leukopenia due to endothelial adherence. After the introduction ofbiocompatible membranes, only CD16 + (i.e. CD14 ++ CD16 + and CD]4 (+) CD16 + ) monocytes showed an impressive transient intra-dialytic decrease. Presently, it is unclear whether this CD16 + monocyte drop is detrimental. We investigated whether a prominent intra-dialytic decrease of CD16 + monocytes predicts future cardiovascular (CV) events. Methods. We measured leukocyte and monocyte subpopulations in 70 patients before and 10 min after haemodialysis initiation. Patients were stratified by their intra-dialytic CD14 ++ CD16 + monocyte drop (pre-defined major drop: decline of cell counts at 10 min to 5 0% of pre-dialytic counts). Patients were followed up for 42 ± 2 months; endpoints were CV events and death. Results. Patients with a minor CD14 ++ CD16 + monocyte drop had more CV events than patients with a major drop. In multivariate analysis, a minor CD 14 ++ CD16 + monocyte drop was the strongest independent predictor of future CV events [hazard ratio 2.405 (95% CI 1.192―4.854)]. Conclusions. These data refute the assumption that a prominent intra-dialytic decrease of CD14 ++ CD16 + monocytes is detrimental. Instead, a minor cell drop could mirror CD14 ++ CD16 + monocyte dysfunction, with inadequate migratory reaction towards an immunologic stimulus posed by membrane and tubing contact.

  • cd14 CD16 monocytes in coronary artery disease and their relationship to serum tnf α levels
    Thrombosis and Haemostasis, 2004
    Co-Authors: Axel Schlitt, Gunnar H. Heine, Stefan Blankenberg, Christine Espinolaklein, Joern F Dopheide, Christoph Bickel, Karl J Lackner, Juergen Meyer, Harald Darius, Hans J Rupprecht
    Abstract:

    Monocytes play a central role in the inflammatory disease atherosclerosis. CD14+CD16+ monocytes are considered proinflammatory monocytes, as they have an increased capacity to produce proinflammatory cytokines, such as TNF-α, and are elevated in various inflammatory diseases.We hypothesized that patients with coronary artery disease (CAD) have increased levels of CD14+CD16+ monocytes, and that CD14+CD16+ monocytes are associated with inflammation markers. We investigated CD14+CD16+ monocytes in 247 patients with CAD and 61 control subjects using flow cytometry. In addition serum concentrations of TNF-α, IL-6, and Hs-CRP were assessed. Patients with CAD had higher levels of CD14+CD16+ monocytes than controls (13.6% versus 11.4%; p

Kohei Ishibashi - One of the best experts on this subject based on the ideXlab platform.

  • acute phase glucose fluctuation is negatively correlated with myocardial salvage after acute myocardial infarction
    Circulation, 2014
    Co-Authors: Ikuko Teraguchi, Yuichi Ozaki, Toshio Imanishi, Yasutsugu Shiono, Takashi Tanimoto, Kohei Ishibashi, Minoru Ueyama, Makoto Orii, Kunihiro Shimamura, Takashi Yamano
    Abstract:

    BACKGROUND It remains unclear whether glycemic fluctuation immediately after acute myocardial infarction (AMI) can affect myocardial damage. This study investigated the impact of glucose fluctuation on myocardial salvage following successful recanalization of primary AMI. METHODS AND RESULTS A total of 36 consecutive patients with AMI were studied. Glycemic variability, as indicated by the mean amplitude of glycemic excursion (MAGE), was measured on a continuous glucose monitoring system. Three subsets (CD14(+)CD16(-), CD14(++)CD16(+) and CD14(+-)CD16(+)) were measured on flow cytometry 1, 2, 3, 4 and 5 days after AMI onset. A 2-h oral glucose test was performed in 23 patients who had no previous diagnosis of diabetes and/or glycated hemoglobin <6.5%, after the onset of AMI at 2 weeks. Plasma active glucagon-like peptide (GLP)-1 level was measured in each sample. The extent of myocardial salvage 7 days after AMI was evaluated on cardiovascular magnetic resonance imaging. MAGE and the peak CD14(+)CD16(-) monocyte level were significantly negatively correlated with myocardial salvage index (MSI). MAGE was significantly correlated with peak CD14(+)CD16(-) monocyte level. Of interest, plasma GLP-1 level was significantly positively correlated with MSI and significantly negatively correlated with MAGE. CONCLUSIONS Glucose fluctuations during the acute phase of AMI affect MSI, indicating that manipulation of glucose variability from peak to nadir might be a potential therapeutic target for salvaging ischemic damage.

  • association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pectoris
    Atherosclerosis, 2010
    Co-Authors: Toshio Imanishi, Kenichi Komukai, Takashi Tanimoto, Hiroto Tsujioka, Hideyuki Ikejima, Akio Kuroi, Kohei Ishibashi, Yasushi Ino, Tatsuya Takeshita, Takashi Akasaka
    Abstract:

    Abstract Objectives We examined whether distinct monocyte subsets relate in specific ways to coronary fibrous cap thickness (FCT) in patients with unstable angina pectoris (UAP). Methods Forty patients with UAP who underwent percutaneous coronary intervention were enrolled in this study. The changes in the non-culprit FCT were assessed by optical coherence tomography (OCT) at baseline and after 9 months. The distinct monocyte subsets (CD14 + CD16 − CCR2 + and CD14 + CD16 + CX3CR1 + ) were measured by flow cytometry. Results The percent change in FCT showed significantly negative correlation with the percent changes in CD14 + CD16 + CX3CR1 + monocytes, but not CD14 + CD16 − CCR2 + monocytes. In addition, the percent change in CD14 + CD16 + CX3CR1 + monocytes was significantly decreased in the group of patients who received statin treatment compared with the group of patients who did not. Of interest, there was a close relationship between CD14 + CD16 + CX3CR1 + monocytes and levels of C-reactive protein, but not lipid profiles, including low-density lipoprotein cholesterol and low-/high-density lipoprotein cholesterol ratio. Conclusions CD14 + CD16 + CX3CR1 + monocytes may have a role in coronary plaque vulnerability.

  • association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64 slice multidetector computed tomography in patients with stable angina pectoris
    Atherosclerosis, 2010
    Co-Authors: Manabu Kashiwagi, Yuichi Ozaki, Toshio Imanishi, Kenichi Komukai, Takashi Tanimoto, Hiroto Tsujioka, Hideyuki Ikejima, Akio Kuroi, Kohei Ishibashi, Yasushi Ino
    Abstract:

    Abstract Objective The aim of the present study was to examine the relation between monocyte subsets and the presence, extent, and vulnerability characteristics of non-calcified coronary plaques (NCPs) as assessed by multidetector computed tomography (MDCT). Methods We studied 73 patients with stable angina pectoris who underwent MDCT. Two monocyte subsets (CD14 + CD16 − and CD14 + CD16 + ) were measured by flow cytometry. Coronary artery plaques were assessed by 64-slice MDCT. We defined NCP vulnerability according to the presence of positive remodeling (remodeling index > 1.05) and/or low CT attenuation plaques ( Results A total of 40 (55%) patients had identifiable vulnerable plaques. The relative proportion of CD14 + CD16 + monocytes was significantly greater in patients with 1 or multiple vulnerable plaques than in patients with no vulnerable plaques or control (healthy) subjects. In addition, the relative proportion of CD14 + CD16 + monocytes was positively correlated with remodeling index ( r  = 0.40, P r  = −0.34, P Conclusion The present results suggest that an increased subset of CD14 + CD16 + monocytes is related to coronary plaque vulnerability in patients with stable angina pectoris.

  • impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction
    Journal of the American College of Cardiology, 2009
    Co-Authors: Hiroto Tsujioka, Toshio Imanishi, Takashi Tanimoto, Hironori Kitabata, Hideyuki Ikejima, Akio Kuroi, Shigeho Takarada, Keishi Okochi, Yu Arita, Kohei Ishibashi
    Abstract:

    Objectives We examined whether distinct monocyte subsets contribute in specific ways to myocardial salvage in patients with acute myocardial infarction (AMI). Background Recent studies have shown that monocytes in human peripheral blood are heterogeneous. Methods We studied 36 patients with primary AMI. Peripheral blood sampling was performed 1, 2, 3, 4, 5, 8, and 12 days after AMI onset. Two monocyte subsets (CD14+CD16−and CD14+CD16+) were measured by flow cytometry. The extent of myocardial salvage 7 days after AMI was evaluated by cardiovascular magnetic resonance imaging as the difference between myocardium at risk (T2-weighted hyperintense lesion) and myocardial necrosis (delayed gadolinium enhancement). Cardiovascular magnetic resonance imaging was also performed 6 months after AMI. Results Circulating CD14+CD16−and CD14+CD16+monocytes increased in AMI patients, peaking on days 3 and 5 after onset, respectively. Importantly, the peak levels of CD14+CD16−monocytes, but not those of CD14+CD16+monocytes, were significantly negatively associated with the extent of myocardial salvage. We also found that the peak levels of CD14+CD16−monocytes, but not those of CD14+CD16+monocytes, were negatively correlated with recovery of left ventricular ejection fraction 6 months after infarction. Conclusions The peak levels of CD14+CD16−monocytes affect both the extent of myocardial salvage and the recovery of left ventricular function after AMI, indicating that the manipulation of monocyte heterogeneity could be a novel therapeutic target for salvaging ischemic damage.