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R J Shaw - One of the best experts on this subject based on the ideXlab platform.
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increase in interleukin il 1β and il 6 in bronchoalveolar Lavage Fluid obtained from infants with chronic lung disease of prematurity
Pediatric Research, 1996Co-Authors: S Kotecha, M Silverman, L Wilson, A Wangoo, R J ShawAbstract:Chronic lung disease (CLD) of prematurity is associated with an initial increase in pulmonary neutrophils followed by pulmonary fibrosis. We determined whether the proinflammatory cytokines, IL-1β and IL-6, were increased in the bronchoalveolar Lavage Fluid obtained from nine infants(median gestation 25 wk, birthweight 820 g) who developed CLD, seven (28 wk, 1110 g) who recovered from the respiratory distress syndrome (RDS), and four(38 wk, 2690 g) control infants. IL-1β and IL-6 protein were both increased in the bronchoalveolar Lavage Fluid from the CLD groups when compared with the RDS and control groups. This difference for both the cytokines was most marked on d 10 of age, when results from infants with and without CLD were compared (IL-1β, 4.6 versus 1.1 ng/mL,p < 0.05; and IL-6, 9.5 versus 1.5 ng/mL, p< 0.05). Immunocytochemistry of Lavage cells for IL-1β, IL-6, and IL-8 protein showed alveolar macrophages to contain all three cytokines, with lesser staining evident in neutrophils, and in epithelial cells occasionally obtained by Lavage. The contribution of alveolar macrophages and luminal cells to the increase in IL-6 and IL-1 was determined by performing semiquantitative reverse transcription-polymerase chain reactions on RNA extracted from Lavage cells. IL-6 mRNA expression was increased in Lavage cells from the CLD infants when compared with the RDS group. However, the expression for IL-1β and IL-8 mRNA was similar in both groups. These results suggest that IL-1β, IL-6, and IL-8 may contribute to the pathogenesis of CLD, and that, in CLD, IL-6 may be produced by cells within the air spaces.
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increase in interleukin 8 and soluble intercellular adhesion molecule 1 in bronchoalveolar Lavage Fluid from premature infants who develop chronic lung disease
Archives of Disease in Childhood-fetal and Neonatal Edition, 1995Co-Authors: S Kotecha, B Chan, N Azam, M Silverman, R J ShawAbstract:Interleukin-8 (IL-8), soluble intercellular adhesion molecule-1 (sICAM), elastase and neutrophils were assessed in bronchoalveolar Lavage Fluid from nine infants who developed chronic lung disease (CLD) after respiratory distress syndrome (RDS), seven who had recovered from RDS, and in four control infants. IL-8, sICAM, elastase and neutrophils in bronchoalveolar Lavage Fluid were increased in the CLD group, the differences being most pronounced at 10 days of age. When babies with and without CLD were compared at 10 days of age, bronchoalveolar Lavage Fluid from the babies with CLD had significantly increased IL-8 (114.0 vs 12.7 ng/ml), sICAM (19.0 vs 1.1 micrograms/ml), elastase (6.9 vs 0.9 micrograms/ml) and neutrophils (1.9 vs 0.4 x 10(9)/l). In serum the increased concentration of IL-8 observed at birth in the CLD (247 pg/ml) and RDS (192 pg/ml) groups decreased over three weeks to the concentrations observed in the controls (
Johan Grunewald - One of the best experts on this subject based on the ideXlab platform.
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Altered microRNA profiles in bronchoalveolar Lavage Fluid exosomes in asthmatic patients
The Journal of allergy and clinical immunology, 2013Co-Authors: Bettina Levänen, Johan Grunewald, Nirav R. Bhakta, Patricia Torregrosa Paredes, Rebecca Barbeau, Stefanie Hiltbrunner, Joshua L. Pollack, C. Magnus Sköld, Magnus Svartengren, Susanne GabrielssonAbstract:Background Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge. Objective To investigate alterations in bronchoalveolar Lavage Fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure. Methods Exosomes were isolated from BALF from healthy control subjects (n = 10) and patients with mild intermittent asthma (n = 10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR. Results were analyzed by using multivariate modeling. Results The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q 2 = 0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles. Conclusion These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.
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bronchoalveolar Lavage Fluid exosomes contribute to cytokine and leukotriene production in allergic asthma
Allergy, 2012Co-Authors: Torregrosa P Paredes, Johan Grunewald, Julia Esser, Charlotte Admyre, Magnus Nord, Q K Rahman, Ana Lukic, Olof Radmark, R Gronneberg, Anders EklundAbstract:Background Leukotrienes (LTs) are potent pro-inflammatory mediators involved in asthma. Exosomes, nanosized vesicles released from various cells, can stimulate or down-regulate immune responses, depending on the state and nature of the originating cell. We have recently shown an altered exosome profile in bronchoalveolar Lavage Fluid (BALF) of patients with sarcoidosis, but their role in asthma is unknown. Our aims were to investigate whether exosomes from BALF have LT biosynthetic capacity and to explore phenotypic and functional characteristics of BALF exosomes in asthma. Methods Bronchoalveolar Lavage Fluid exosomes were collected from healthy individuals (n = 13) and patients with mild allergic asthma to birch pollen (n = 12) before and after birch allergen provocation. Exosomes were characterized by flow cytometry and Western blot. Their capacity to induce IL-8 and LT production in the human bronchial epithelial cell (BEC) line 16HB14o- was measured by ELISA and reverse-phase HPLC, respectively. Results Compared to BALF exosomes from healthy individuals, BALF exosomes from asthmatics displayed higher levels of exosome-associated markers, such as the tetraspanins CD63 and CD81 and the scavenger receptor CD36. No major differences were observed between BALF exosomes from before and after allergen provocation. Furthermore, we show that BALF exosomes contain enzymes for LT biosynthesis. The effect of exosomes to promote LTC4 and IL-8 release in BEC was significantly increased for exosomes from asthmatics, and the CysLT1 receptor antagonist Montelukast reduced exosome-induced IL-8 secretion. Conclusions Bronchoalveolar Lavage Fluid exosomes from asthmatic and healthy individuals exhibit distinct phenotypes and functions. BALF exosomes from asthmatics might contribute to subclinical inflammation by increasing cytokine and LTC4 generation in airway epithelium.
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proinflammatory exosomes in bronchoalveolar Lavage Fluid of patients with sarcoidosis
Thorax, 2010Co-Authors: Khaleda Rahman Qazi, Anders Eklund, Johan Grunewald, Patricia Torregrosa Paredes, Benita Dahlberg, Susanne GabrielssonAbstract:Background Sarcoidosis is a systemic disease of unknown aetiology characterised by granuloma formation and the presence of interferon g (IFNg)-producing T cells that cause inflammation and tissue damage in multiple organs, especially the lung. Exosomes are nano-sized immunomodulatory vesicles of endosomal origin released from a diverse range of cells and are also found in physiological Fluids including bronchoalveolar Lavage Fluid (BALF) from healthy individuals. Objective To investigate whether exosomes are enriched in the lungs of patients with sarcoidosis compared with healthy individuals and whether they could contribute to pathogenesis. Design BALF exosomes from patients with sarcoidosis (n¼36) and healthy controls (n¼14) were compared by electron microscopy, flow cytometry, western blot analysis and mass spectrometry. BALF exosomes were incubated with autologous peripheral blood mononuclear cells (PBMCs) or the human bronchial epithelial cell line 16HBE14o-. Cytokines were measured by ELISPOT and ELISA. Results BALF from patients with sarcoidosis showed increased levels of exosomes compared with healthy individuals. Exosomes from patients showed significantly higher expression of MHC class I and II, tetraspanins CD9, CD63 and CD81 as well as neuregulin-1, known to be associated with cancer progression. Furthermore, BALF exosomes from patients induced significantly higher IFNg and interleukin (IL)-13 production in autologous PBMCs compared with healthy individuals and could also stimulate IL-8 production from epithelial cells. Conclusion The results indicate for the first time a role for exosomes in human lung disease with possible contributions to the initiation and progression of inflammation in sarcoidosis. This suggests that exosomes may be a new potential target for the clinical treatment of lung diseases.
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antibacterial components in bronchoalveolar Lavage Fluid from healthy individuals and sarcoidosis patients
American Journal of Respiratory and Critical Care Medicine, 1999Co-Authors: Birgitta Agerberth, Anders Eklund, Johan Grunewald, Esmeralda Castanosvelez, Berit Olsson, Hans Jornvall, Hans Wigzell, Gudmundur H GudmundssonAbstract:Antibacterial peptides and proteins are an integral part of the epithelial defense barrier that provides immediate protection against bacterial invasion. In humans, α -defensins are mainly bactericidal effectors in circulating granulocytes, β -defensin-1 is synthesized in epithelial cells, and LL-37 is produced in granulocytes but is also induced in skin epithelia during inflammation. To investigate the importance of these defense effectors in disease, we analyzed bronchoalveolar Lavage Fluid (BALF) for bactericidal activity. Antibacterial activity was found in BALF material from healthy individuals and sarcoidosis patients, with enhanced activity in BALF from the patients. The activity was present as several antibacterial components, of which we have so far characterized LL-37, lysozyme, α -defensins, and antileukoprotease. In addition, the antibacterial peptide LL-37 was located in alveolar macrophages, bronchial epithelial cells, and bronchial glands, suggesting that it has a defensive role in airway m...
Susanne Gabrielsson - One of the best experts on this subject based on the ideXlab platform.
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Altered microRNA profiles in bronchoalveolar Lavage Fluid exosomes in asthmatic patients
The Journal of allergy and clinical immunology, 2013Co-Authors: Bettina Levänen, Johan Grunewald, Nirav R. Bhakta, Patricia Torregrosa Paredes, Rebecca Barbeau, Stefanie Hiltbrunner, Joshua L. Pollack, C. Magnus Sköld, Magnus Svartengren, Susanne GabrielssonAbstract:Background Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge. Objective To investigate alterations in bronchoalveolar Lavage Fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure. Methods Exosomes were isolated from BALF from healthy control subjects (n = 10) and patients with mild intermittent asthma (n = 10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR. Results were analyzed by using multivariate modeling. Results The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q 2 = 0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles. Conclusion These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.
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proinflammatory exosomes in bronchoalveolar Lavage Fluid of patients with sarcoidosis
Thorax, 2010Co-Authors: Khaleda Rahman Qazi, Anders Eklund, Johan Grunewald, Patricia Torregrosa Paredes, Benita Dahlberg, Susanne GabrielssonAbstract:Background Sarcoidosis is a systemic disease of unknown aetiology characterised by granuloma formation and the presence of interferon g (IFNg)-producing T cells that cause inflammation and tissue damage in multiple organs, especially the lung. Exosomes are nano-sized immunomodulatory vesicles of endosomal origin released from a diverse range of cells and are also found in physiological Fluids including bronchoalveolar Lavage Fluid (BALF) from healthy individuals. Objective To investigate whether exosomes are enriched in the lungs of patients with sarcoidosis compared with healthy individuals and whether they could contribute to pathogenesis. Design BALF exosomes from patients with sarcoidosis (n¼36) and healthy controls (n¼14) were compared by electron microscopy, flow cytometry, western blot analysis and mass spectrometry. BALF exosomes were incubated with autologous peripheral blood mononuclear cells (PBMCs) or the human bronchial epithelial cell line 16HBE14o-. Cytokines were measured by ELISPOT and ELISA. Results BALF from patients with sarcoidosis showed increased levels of exosomes compared with healthy individuals. Exosomes from patients showed significantly higher expression of MHC class I and II, tetraspanins CD9, CD63 and CD81 as well as neuregulin-1, known to be associated with cancer progression. Furthermore, BALF exosomes from patients induced significantly higher IFNg and interleukin (IL)-13 production in autologous PBMCs compared with healthy individuals and could also stimulate IL-8 production from epithelial cells. Conclusion The results indicate for the first time a role for exosomes in human lung disease with possible contributions to the initiation and progression of inflammation in sarcoidosis. This suggests that exosomes may be a new potential target for the clinical treatment of lung diseases.
Anders Eklund - One of the best experts on this subject based on the ideXlab platform.
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bronchoalveolar Lavage Fluid exosomes contribute to cytokine and leukotriene production in allergic asthma
Allergy, 2012Co-Authors: Torregrosa P Paredes, Johan Grunewald, Julia Esser, Charlotte Admyre, Magnus Nord, Q K Rahman, Ana Lukic, Olof Radmark, R Gronneberg, Anders EklundAbstract:Background Leukotrienes (LTs) are potent pro-inflammatory mediators involved in asthma. Exosomes, nanosized vesicles released from various cells, can stimulate or down-regulate immune responses, depending on the state and nature of the originating cell. We have recently shown an altered exosome profile in bronchoalveolar Lavage Fluid (BALF) of patients with sarcoidosis, but their role in asthma is unknown. Our aims were to investigate whether exosomes from BALF have LT biosynthetic capacity and to explore phenotypic and functional characteristics of BALF exosomes in asthma. Methods Bronchoalveolar Lavage Fluid exosomes were collected from healthy individuals (n = 13) and patients with mild allergic asthma to birch pollen (n = 12) before and after birch allergen provocation. Exosomes were characterized by flow cytometry and Western blot. Their capacity to induce IL-8 and LT production in the human bronchial epithelial cell (BEC) line 16HB14o- was measured by ELISA and reverse-phase HPLC, respectively. Results Compared to BALF exosomes from healthy individuals, BALF exosomes from asthmatics displayed higher levels of exosome-associated markers, such as the tetraspanins CD63 and CD81 and the scavenger receptor CD36. No major differences were observed between BALF exosomes from before and after allergen provocation. Furthermore, we show that BALF exosomes contain enzymes for LT biosynthesis. The effect of exosomes to promote LTC4 and IL-8 release in BEC was significantly increased for exosomes from asthmatics, and the CysLT1 receptor antagonist Montelukast reduced exosome-induced IL-8 secretion. Conclusions Bronchoalveolar Lavage Fluid exosomes from asthmatic and healthy individuals exhibit distinct phenotypes and functions. BALF exosomes from asthmatics might contribute to subclinical inflammation by increasing cytokine and LTC4 generation in airway epithelium.
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proinflammatory exosomes in bronchoalveolar Lavage Fluid of patients with sarcoidosis
Thorax, 2010Co-Authors: Khaleda Rahman Qazi, Anders Eklund, Johan Grunewald, Patricia Torregrosa Paredes, Benita Dahlberg, Susanne GabrielssonAbstract:Background Sarcoidosis is a systemic disease of unknown aetiology characterised by granuloma formation and the presence of interferon g (IFNg)-producing T cells that cause inflammation and tissue damage in multiple organs, especially the lung. Exosomes are nano-sized immunomodulatory vesicles of endosomal origin released from a diverse range of cells and are also found in physiological Fluids including bronchoalveolar Lavage Fluid (BALF) from healthy individuals. Objective To investigate whether exosomes are enriched in the lungs of patients with sarcoidosis compared with healthy individuals and whether they could contribute to pathogenesis. Design BALF exosomes from patients with sarcoidosis (n¼36) and healthy controls (n¼14) were compared by electron microscopy, flow cytometry, western blot analysis and mass spectrometry. BALF exosomes were incubated with autologous peripheral blood mononuclear cells (PBMCs) or the human bronchial epithelial cell line 16HBE14o-. Cytokines were measured by ELISPOT and ELISA. Results BALF from patients with sarcoidosis showed increased levels of exosomes compared with healthy individuals. Exosomes from patients showed significantly higher expression of MHC class I and II, tetraspanins CD9, CD63 and CD81 as well as neuregulin-1, known to be associated with cancer progression. Furthermore, BALF exosomes from patients induced significantly higher IFNg and interleukin (IL)-13 production in autologous PBMCs compared with healthy individuals and could also stimulate IL-8 production from epithelial cells. Conclusion The results indicate for the first time a role for exosomes in human lung disease with possible contributions to the initiation and progression of inflammation in sarcoidosis. This suggests that exosomes may be a new potential target for the clinical treatment of lung diseases.
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antibacterial components in bronchoalveolar Lavage Fluid from healthy individuals and sarcoidosis patients
American Journal of Respiratory and Critical Care Medicine, 1999Co-Authors: Birgitta Agerberth, Anders Eklund, Johan Grunewald, Esmeralda Castanosvelez, Berit Olsson, Hans Jornvall, Hans Wigzell, Gudmundur H GudmundssonAbstract:Antibacterial peptides and proteins are an integral part of the epithelial defense barrier that provides immediate protection against bacterial invasion. In humans, α -defensins are mainly bactericidal effectors in circulating granulocytes, β -defensin-1 is synthesized in epithelial cells, and LL-37 is produced in granulocytes but is also induced in skin epithelia during inflammation. To investigate the importance of these defense effectors in disease, we analyzed bronchoalveolar Lavage Fluid (BALF) for bactericidal activity. Antibacterial activity was found in BALF material from healthy individuals and sarcoidosis patients, with enhanced activity in BALF from the patients. The activity was present as several antibacterial components, of which we have so far characterized LL-37, lysozyme, α -defensins, and antileukoprotease. In addition, the antibacterial peptide LL-37 was located in alveolar macrophages, bronchial epithelial cells, and bronchial glands, suggesting that it has a defensive role in airway m...
P A Forsythe - One of the best experts on this subject based on the ideXlab platform.
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increased mcp 1 rantes and mip 1α in bronchoalveolar Lavage Fluid of allergic asthmatic patients
American Journal of Respiratory and Critical Care Medicine, 1996Co-Authors: Rafeul Alam, J York, Michael Boyars, Susan Stafford, J A Grant, P A ForsytheAbstract:Chemokines are cytokines that induce chemotaxis of inflammatory cells. We studied the presence of chemokines in bronchoalveolar Lavage Fluid (BALF) obtained from nine allergic asthmatic patients and six nonsmoking normal individuals. The cells were pelleted, and ribonucleic acid (RNA) was extracted by using RNAzol B. BALF was assayed for monocyte chemoattractant protein-1 (MCP-1), regulated upon activation in normal T cells, expressed, probably secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha) and interleukin-8 (IL-8) by enzyme-linked immunosorbent assay (ELISA). The levels of MCP-1, RANTES, and MIP-1alpha were significantly higher in the asthma patients than in the control subjects (p<0.04). The concentrations of RANTES and MCP-1 correlated with the lymphocyte count in the BAL specimens (r = 0.61 and 0.68, respectively). BALF showed eosinophil chemotactic activity in vitro that was blocked by anti-RANTES and anti-MCP-3 antibodies. The total cellular RNA was reverse-transcribed and th...
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increased mcp 1 rantes and mip 1alpha in bronchoalveolar Lavage Fluid of allergic asthmatic patients
American Journal of Respiratory and Critical Care Medicine, 1996Co-Authors: Rafeul Alam, J York, Michael Boyars, Susan Stafford, J A Grant, P A Forsythe, Jana Lee, Tommy C Sim, Nobuo IdaAbstract:Chemokines are cytokines that induce chemotaxis of inflammatory cells. We studied the presence of chemokines in bronchoalveolar Lavage Fluid (BALF) obtained from nine allergic asthmatic patients and six nonsmoking normal individuals. The cells were pelleted, and ribonucleic acid (RNA) was extracted by using RNAzol B. BALF was assayed for monocyte chemoattractant protein-1 (MCP-1), regulated upon activation in normal T cells, expressed, probably secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha) and interleukin-8 (IL-8) by enzyme-linked immunosorbent assay (ELISA). The levels of MCP-1, RANTES, and MIP-1alpha were significantly higher in the asthma patients than in the control subjects (p<0.04). The concentrations of RANTES and MCP-1 correlated with the lymphocyte count in the BAL specimens (r = 0.61 and 0.68, respectively). BALF showed eosinophil chemotactic activity in vitro that was blocked by anti-RANTES and anti-MCP-3 antibodies. The total cellular RNA was reverse-transcribed and th...