The Experts below are selected from a list of 13311 Experts worldwide ranked by ideXlab platform
Guiying Cheng - One of the best experts on this subject based on the ideXlab platform.
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the α 1 3 fucosyltransferases fuct iv and fuct vii exert collaborative control over selectin dependent Leukocyte Recruitment and lymphocyte homing
Immunity, 2001Co-Authors: Jonathon W Homeister, Aron D Thall, Bronia Petryniak, Petr Malý, Clare E Rogers, Peter L Smith, Robert Kelly, Kevin M Gersten, Sanaz Askari, Guiying ChengAbstract:Abstract E-, P-, and L-selectin counterreceptor activities, Leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by α(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent Leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in Leukocyte Recruitment is contradictory and incomplete. We show here that inflammation-dependent Leukocyte Recruitment retained in FucT-VII deficiency is extinguished in FucT-IV −/− / FucT-VII −/− mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII −/− mice is revoked in FucT-IV −/− / FucT-VII −/− mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of Leukocyte Recruitment and lymphocyte homing.
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the α 1 3 fucosyltransferases fuct iv and fuct vii exert collaborative control over selectin dependent Leukocyte Recruitment and lymphocyte homing
Immunity, 2001Co-Authors: Jonathon W Homeister, Aron D Thall, Bronia Petryniak, Petr Malý, Clare E Rogers, Peter L Smith, Robert Kelly, Kevin M Gersten, Sanaz Askari, Guiying ChengAbstract:Abstract E-, P-, and L-selectin counterreceptor activities, Leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by α(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent Leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in Leukocyte Recruitment is contradictory and incomplete. We show here that inflammation-dependent Leukocyte Recruitment retained in FucT-VII deficiency is extinguished in FucT-IV −/− / FucT-VII −/− mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII −/− mice is revoked in FucT-IV −/− / FucT-VII −/− mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of Leukocyte Recruitment and lymphocyte homing.
Jonathon W Homeister - One of the best experts on this subject based on the ideXlab platform.
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the α 1 3 fucosyltransferases fuct iv and fuct vii exert collaborative control over selectin dependent Leukocyte Recruitment and lymphocyte homing
Immunity, 2001Co-Authors: Jonathon W Homeister, Aron D Thall, Bronia Petryniak, Petr Malý, Clare E Rogers, Peter L Smith, Robert Kelly, Kevin M Gersten, Sanaz Askari, Guiying ChengAbstract:Abstract E-, P-, and L-selectin counterreceptor activities, Leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by α(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent Leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in Leukocyte Recruitment is contradictory and incomplete. We show here that inflammation-dependent Leukocyte Recruitment retained in FucT-VII deficiency is extinguished in FucT-IV −/− / FucT-VII −/− mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII −/− mice is revoked in FucT-IV −/− / FucT-VII −/− mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of Leukocyte Recruitment and lymphocyte homing.
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the α 1 3 fucosyltransferases fuct iv and fuct vii exert collaborative control over selectin dependent Leukocyte Recruitment and lymphocyte homing
Immunity, 2001Co-Authors: Jonathon W Homeister, Aron D Thall, Bronia Petryniak, Petr Malý, Clare E Rogers, Peter L Smith, Robert Kelly, Kevin M Gersten, Sanaz Askari, Guiying ChengAbstract:Abstract E-, P-, and L-selectin counterreceptor activities, Leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by α(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent Leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in Leukocyte Recruitment is contradictory and incomplete. We show here that inflammation-dependent Leukocyte Recruitment retained in FucT-VII deficiency is extinguished in FucT-IV −/− / FucT-VII −/− mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII −/− mice is revoked in FucT-IV −/− / FucT-VII −/− mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of Leukocyte Recruitment and lymphocyte homing.
Ali Hafezimoghadam - One of the best experts on this subject based on the ideXlab platform.
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pitavastatin prevents nmda induced retinal ganglion cell death by suppressing Leukocyte Recruitment
Journal of Neurochemistry, 2007Co-Authors: Toru Nakazawa, Hidetoshi Takahashi, Kazuaki Nishijima, Masahiko Shimura, Nobuo Fuse, Makoto Tamai, Ali HafezimoghadamAbstract:Excitotoxicity is a major cause of retinal ganglion cell (RGC) death during ischemic diseases such as vessel occlusion and diabetic retinopathy. However, the underlying mechanisms are not well understood. Statins, inhibitors of the HMG-CoA reductase, have neuroprotective effects in addition to their original role in lowering cholesterol. We hypothesize that pitavastatin, a recently introduced potent statin, is protective against N-methyl-d-aspartic acid (NMDA)-induced RGC death. Pitavastatin, administered by gavage, abolished NMDA-induced loss of RGCs. To elucidate the mechanisms underlying the neuroprotective effect of pitavastatin, we investigated its impact on inflammation. NMDA increased the expression of interleukin-1β and TNF-α, and endothelial adhesion molecules, including ICAM-1, and induced Leukocyte accumulation in the retinal vessels. Pitavastatin significantly reduced NMDA-induced Leukocyte accumulation and up-regulation of endothelial adhesion molecules, whereas cytokine expression was unaffected. Systemic blockade of ICAM-1 in wild-type mice or absence of CD18 in gene-deficient (CD18–/–) mice significantly suppressed NMDA-induced Leukocyte accumulation and RGC death. These findings suggest a novel and causative role for inflammatory Leukocyte Recruitment in NMDA-induced excitotoxicity. Furthermore, we show the novel neuroprotective effect of statins against excitotoxicity-induced RGC death. Statins or other anti-inflammatory agents may thus have therapeutic benefits in excitotoxicity-associated neuronal diseases through blockade of Leukocyte Recruitment.
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pitavastatin prevents nmda induced retinal ganglion cell death by suppressing Leukocyte Recruitment
Journal of Neurochemistry, 2007Co-Authors: Toru Nakazawa, Hidetoshi Takahashi, Kazuaki Nishijima, Masahiko Shimura, Nobuo Fuse, Makoto Tamai, Ali HafezimoghadamAbstract:Excitotoxicity is a major cause of retinal ganglion cell (RGC) death during ischemic diseases such as vessel occlusion and diabetic retinopathy. However, the underlying mechanisms are not well understood. Statins, inhibitors of the HMG-CoA reductase, have neuroprotective effects in addition to their original role in lowering cholesterol. We hypothesize that pitavastatin, a recently introduced potent statin, is protective against N-methyl-d-aspartic acid (NMDA)-induced RGC death. Pitavastatin, administered by gavage, abolished NMDA-induced loss of RGCs. To elucidate the mechanisms underlying the neuroprotective effect of pitavastatin, we investigated its impact on inflammation. NMDA increased the expression of interleukin-1beta and TNF-alpha, and endothelial adhesion molecules, including ICAM-1, and induced Leukocyte accumulation in the retinal vessels. Pitavastatin significantly reduced NMDA-induced Leukocyte accumulation and up-regulation of endothelial adhesion molecules, whereas cytokine expression was unaffected. Systemic blockade of ICAM-1 in wild-type mice or absence of CD18 in gene-deficient (CD18(-/-)) mice significantly suppressed NMDA-induced Leukocyte accumulation and RGC death. These findings suggest a novel and causative role for inflammatory Leukocyte Recruitment in NMDA-induced excitotoxicity. Furthermore, we show the novel neuroprotective effect of statins against excitotoxicity-induced RGC death. Statins or other anti-inflammatory agents may thus have therapeutic benefits in excitotoxicity-associated neuronal diseases through blockade of Leukocyte Recruitment.
Toru Nakazawa - One of the best experts on this subject based on the ideXlab platform.
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pitavastatin prevents nmda induced retinal ganglion cell death by suppressing Leukocyte Recruitment
Journal of Neurochemistry, 2007Co-Authors: Toru Nakazawa, Hidetoshi Takahashi, Kazuaki Nishijima, Masahiko Shimura, Nobuo Fuse, Makoto Tamai, Ali HafezimoghadamAbstract:Excitotoxicity is a major cause of retinal ganglion cell (RGC) death during ischemic diseases such as vessel occlusion and diabetic retinopathy. However, the underlying mechanisms are not well understood. Statins, inhibitors of the HMG-CoA reductase, have neuroprotective effects in addition to their original role in lowering cholesterol. We hypothesize that pitavastatin, a recently introduced potent statin, is protective against N-methyl-d-aspartic acid (NMDA)-induced RGC death. Pitavastatin, administered by gavage, abolished NMDA-induced loss of RGCs. To elucidate the mechanisms underlying the neuroprotective effect of pitavastatin, we investigated its impact on inflammation. NMDA increased the expression of interleukin-1β and TNF-α, and endothelial adhesion molecules, including ICAM-1, and induced Leukocyte accumulation in the retinal vessels. Pitavastatin significantly reduced NMDA-induced Leukocyte accumulation and up-regulation of endothelial adhesion molecules, whereas cytokine expression was unaffected. Systemic blockade of ICAM-1 in wild-type mice or absence of CD18 in gene-deficient (CD18–/–) mice significantly suppressed NMDA-induced Leukocyte accumulation and RGC death. These findings suggest a novel and causative role for inflammatory Leukocyte Recruitment in NMDA-induced excitotoxicity. Furthermore, we show the novel neuroprotective effect of statins against excitotoxicity-induced RGC death. Statins or other anti-inflammatory agents may thus have therapeutic benefits in excitotoxicity-associated neuronal diseases through blockade of Leukocyte Recruitment.
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pitavastatin prevents nmda induced retinal ganglion cell death by suppressing Leukocyte Recruitment
Journal of Neurochemistry, 2007Co-Authors: Toru Nakazawa, Hidetoshi Takahashi, Kazuaki Nishijima, Masahiko Shimura, Nobuo Fuse, Makoto Tamai, Ali HafezimoghadamAbstract:Excitotoxicity is a major cause of retinal ganglion cell (RGC) death during ischemic diseases such as vessel occlusion and diabetic retinopathy. However, the underlying mechanisms are not well understood. Statins, inhibitors of the HMG-CoA reductase, have neuroprotective effects in addition to their original role in lowering cholesterol. We hypothesize that pitavastatin, a recently introduced potent statin, is protective against N-methyl-d-aspartic acid (NMDA)-induced RGC death. Pitavastatin, administered by gavage, abolished NMDA-induced loss of RGCs. To elucidate the mechanisms underlying the neuroprotective effect of pitavastatin, we investigated its impact on inflammation. NMDA increased the expression of interleukin-1beta and TNF-alpha, and endothelial adhesion molecules, including ICAM-1, and induced Leukocyte accumulation in the retinal vessels. Pitavastatin significantly reduced NMDA-induced Leukocyte accumulation and up-regulation of endothelial adhesion molecules, whereas cytokine expression was unaffected. Systemic blockade of ICAM-1 in wild-type mice or absence of CD18 in gene-deficient (CD18(-/-)) mice significantly suppressed NMDA-induced Leukocyte accumulation and RGC death. These findings suggest a novel and causative role for inflammatory Leukocyte Recruitment in NMDA-induced excitotoxicity. Furthermore, we show the novel neuroprotective effect of statins against excitotoxicity-induced RGC death. Statins or other anti-inflammatory agents may thus have therapeutic benefits in excitotoxicity-associated neuronal diseases through blockade of Leukocyte Recruitment.
Paul Kubes - One of the best experts on this subject based on the ideXlab platform.
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modulating Leukocyte Recruitment in inflammation
The Journal of Allergy and Clinical Immunology, 2007Co-Authors: Margaret M Kelly, John M Hwang, Paul KubesAbstract:Much information has been obtained regarding how white cells are recruited in the microcirculation to sites of inflammation. In this review we summarize the Leukocyte Recruitment cascade, highlighting the molecular mechanisms that underlie each of the major steps. Major emphasis is placed on the selectins and integrins and their role in rolling and adhesion. Intraluminal crawling and emigration are also briefly discussed. In addition, we summarize some of the data that implicate these molecules in eosinophil Recruitment in animal models of asthma and in lymphocyte Recruitment in skin contact sensitivity. There is a growing body of evidence to suggest that Leukocyte Recruitment could be used as an effective means for future therapeutics, and some of these issues are also raised.
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Leukocyte PI3Kγ and PI3Kδ have temporally distinct roles for Leukocyte Recruitment in vivo
Blood, 2007Co-Authors: Lixin Liu, Kamal D. Puri, Josef M. Penninger, Paul KubesAbstract:Phosphoinositide 3-kinases (PI3Ks) have been considered important in Leukocyte motility. PI3Kgamma, the class I(B) PI3K, expressed prominently in Leukocytes and also in endothelial cells, mediates Leukocyte functional responses induced by chemoattractants. To reveal its role in Leukocyte Recruitment, we used intravital microscopy to directly visualize Leukocyte rolling, adhesion, and emigration in postcapillary venules in PI3Kgamma-deficient (PI3Kgamma(-/-)) mice. We report here that PI3Kgamma deficiency had no significant effects on Leukocyte rolling flux or rolling velocity and minor effects on adhesion (30% to 35%) in response to CXC chemokine MIP-2 (CXCL2) or KC (CXCL1). However, Leukocyte emigration was severely impaired in PI3Kgamma(-/-) mice in an early (first 90 minutes) response to MIP-2 or KC. Chimeric mice receiving bone marrow transplants revealed that this early response was entirely dependent upon PI3Kgamma in neutrophils but not parenchymal cells (endothelium and others). Identical responses were observed when endogenous chemokine production was induced by TNFalpha; Leukocyte emigration was reduced in PI3Kgamma(-/-) mice. More prolonged responses to MIP-2 (for 4 to 5 hours) or TNFalpha (6 to 8 hours) were almost entirely PI3Kgamma independent and largely dependent on PI3Kdelta. Our results reveal that Leukocyte emigration response to CXC chemokines is entirely dependent upon PI3Kgamma or PI3Kdelta, but these are nonoverlapping, temporally distinct events in inflamed tissues in vivo.
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Leukocyte Recruitment and the Acute Inflammatory Response
Brain pathology (Zurich Switzerland), 2006Co-Authors: Paul Kubes, Peter A WardAbstract:Leukocyte Recruitment is a hallmark feature of the inflammatory response. This review summarizes the generally accepted paradigm of Leukocyte Recruitment based on studies using intravital microscopy to visualize the microcirculation. The role of selectins and alpha4-integrin in rolling as well as integrin-mediated adhesion is discussed. However, it is becoming increasingly clear that the Recruitment cascade within organs differs and therefore the review also attempts to highlight what is and is not known regarding Leukocyte Recruitment into the brain microvasculature. In the second part of this review, we provide some discussion of mechanisms by which the inflammatory response may be terminated. Particular emphasis on nuclear factor Nf kappaB and how IL10, IL13 and secreted Leukocyte protease inhibitor (SLPI) may impact upon the Nf kappaB-dependent inflammatory response is presented.
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A Requirement for Microglial TLR4 in Leukocyte Recruitment into Brain in Response to Lipopolysaccharide
The Journal of Immunology, 2006Co-Authors: B. M. Lapointe, S. R. Clark, L. Zbytnuik, Paul KubesAbstract:To study the mechanisms involved in Leukocyte Recruitment induced by local bacterial infection within the CNS, we used intravital microscopy to visualize the interaction between Leukocytes and the microvasculature in the brain. First, we showed that intracerebroventricular injection of LPS could cause significant rolling and adhesion of Leukocytes in the brain postcapillary venules of wild-type mice, while negligible Recruitment was observed in TLR4-deficient C57BL/10ScCr mice and CD14 knockout mice, suggesting Recruitment is mediated by TLR4/CD14-bearing cells. Moreover, we observed reduced but not complete inhibition of Recruitment in MyD88 knockout mice, indicating both MyD88-dependent and -independent pathways are involved. The Leukocyte Recruitment responses in chimeric mice with TLR4-positive microglia and endothelium, but TLR4-negative Leukocytes, were comparable to normal wild-type mice, suggesting either endothelium or microglia play a crucial role in the induction of Leukocyte Recruitment. LPS injection induced both microglial and endothelial activation in the CNS. Furthermore, minocycline, an effective inhibitor of microglial activation, completely blocked the rolling and adhesion of Leukocytes in the brain and blocked TNF-alpha production in response to LPS in vivo. Minocycline did not affect activation of endothelium by LPS in vitro. TNFR p55/p75 double knockout mice also exhibited significant reductions in both rolling and adhesion in response to LPS, indicating TNF-alpha signaling is critical for the Leukocyte Recruitment. Our results identify a TLR4 detection system within the blood-brain barrier. The microglia play the role of sentinel cells detecting LPS thereby inducing endothelial activation and leading to efficient Leukocyte Recruitment to the CNS.
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a role for platelets and endothelial selectins in tumor necrosis factor α induced Leukocyte Recruitment in the brain microvasculature
Circulation Research, 2000Co-Authors: Juliana Carvalhotavares, Michael J Hickey, Jamie Hutchison, Jean Michaud, Ian T Sutcliffe, Paul KubesAbstract:Abstract—The mechanisms mediating Leukocyte Recruitment into the cerebral nervous system during inflammation are still poorly understood. The objective of this study was to investigate the leukocyt...