Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymorphonuclear leukocytes (PMN) are directly involved in development of ischemic myocardial injury. Adhesion of PMN to endothelial cells is an initial step that triggers a sequential process leading to acute inflammatory responses. Interaction between P-selectin and its oligosaccharide ligand, sialyl Lewis x (sLex), plays an important role in the early stage of the adhesion. To examine the role of P-selectin in various animal disease models especially in rats, we have cloned rat E- and P-selectin cDNAs and established monoclonal antibodies against these rat selectins. In this report, we describe the generation and characterization of anti-rat P-selectin antibodies (ARPs). These antibodies detect cell surface P-selectin on thrombin-stimulated rat platelets. More importantly, intravenous administration of ARP2-4 reduced infarction developed after 30 min of ischemia followed by 24 h of reperfusion in a rat myocardial injury model. In addition, similar protective effect was also observed by administration of a sLex-oligosaccharide. These results indicate that cell adhesion mediated via P-selectin is involved in the development of ischemia and reperfusion injury in rat heart.
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PMID:Reduction of rat myocardial ischemia and reperfusion injury by sialyl Lewis x oligosaccharide and anti-rat P-selectin antibodies. 884 11

P-selectin is rapidly translocated to the surface of endothelial cells and platelets following exposure to chemical mediators such as histamine, thrombin and complement factors. The Arthus reaction is caused by vascular injury which is initiated by the local deposition of the immune complex followed by the activation of complement and release of chemical mediators. In this report, the role of P-selectin in the early stage of reverse passive Arthus reaction in rat using monoclonal antibodies (mAbs) against rat P-selectin will be investigated. Intravenous administration of the mAb ARP2-4 significantly attenuated paw edema 1 h after challenging it with antigen by 31.5% (1 mg/kg) and 44.7% (3 mg/kg), respectively. Edema formation was also reduced by sulfatide (73.1%, 50 mg/kg) and inositol hexakisphosphate (InsP6) (72.9%, 30 mg/kg), which have been reported to block P-selectin-mediated neutrophil adhesion. Moreover, neutrophil accumulation into the inflammatory site in the Arthus reaction was inhibited by anti-P-selectin mAb. P-selectin expression was detected along vessel walls prior to neutrophil accumulation, as determined by immunohistochemical staining using the antibody. In addition, the expression of P-selectin mRNA was induced 4 h after deposition of immune complex. From these results, we concluded that P-selectin plays an important role in the pathogenesis of the Arthus reaction especially in the early stage by recruiting neutrophils into sites of inflammation.
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PMID:Role of P-selectin in the early stage of the Arthus reaction. 888 60

Endothelial junctions are dynamic structures organized by multi-protein complexes that control monolayer integrity, homeostasis, inflammation, cell migration and angiogenesis. Newly developed methods for both the genetic manipulation of endothelium and microscopy permit time-lapse recordings of fluorescent proteins over long periods of time. Quantitative data analyses require automated methods. We developed a software package, the CellBorderTracker, allowing quantitative analysis of fluorescent-tagged cell junction protein dynamics in time-lapse sequences. The CellBorderTracker consists of the CellBorderExtractor that segments cells and identifies cell boundaries and mapping tools for data extraction. The tool is illustrated by analyzing fluorescent-tagged VE-cadherin the backbone of adherence junctions in endothelium. VE-cadherin displays high dynamics that is forced by junction-associated intermittent lamellipodia (JAIL) that are actin driven and WASP/ARP2/3 complex controlled. The manual segmentation and the automatic one agree to 90 %, a value that indicates high reliability. Based on segmentations, different maps were generated allowing more detailed data extraction. This includes the quantification of protein distribution pattern, the generation of regions of interest, junction displacements, cell shape changes, migration velocities and the visualization of junction dynamics over many hours. Furthermore, we demonstrate an advanced kymograph, the J-kymograph that steadily follows irregular cell junction dynamics in time-lapse sequences for individual junctions at the subcellular level. By using the CellBorderTracker, we demonstrate that VE-cadherin dynamics is quickly arrested upon thrombin stimulation, a phenomenon that was largely due to transient inhibition of JAIL and display a very heterogeneous subcellular and divers VE-cadherin dynamics during intercellular gap formation and resealing.
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PMID:The CellBorderTracker, a novel tool to quantitatively analyze spatiotemporal endothelial junction dynamics at the subcellular level. 2627 69