Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapid translocation of P-selectin (GMP-140) from cytoplasmic granules to the cell membrane of endothelial cells promotes adhesive interactions with neutrophils which, when activated, damage the endothelium. The role of P-selectin in lung vascular endothelial injury in rats after systemic activation of complement by intravenous infusion of cobra venom factor has been assessed. Within 5-10 min after cobra venom factor infusion, the pulmonary vasculature demonstrated immunohistochemical expression of an epitope that reacts with anti-human P-selectin. Monoclonal antibody to human P-selectin blocked in vitro adherence of rat or human platelets (activated with thrombin) to neutrophils and was demonstrated to react with thrombin-activated rat platelets. The antibody did not react with rat neutrophils. In vivo, the antibody had strongly protective effects against cobra venom factor-induced pulmonary vascular injury as determined by permeability changes and hemorrhage. In parallel, lung myeloperoxidase content was greatly reduced and, by transmission electron microscopy, there was markedly diminished adherence of neutrophils to the pulmonary vascular endothelium and much diminished injury of endothelial cells, as defined by hemorrhage. These data indicate that anti-human P-selectin reacts with a pulmonary vascular antigen in rats and that this antigen is essential for the full expression of lung injury.
...
PMID:Neutrophil-dependent acute lung injury. Requirement for P-selectin (GMP-140). 138 77

Recombinant selectin chimeric molecules featuring the joining of the extracellular domains of L-, P-, and E-selectin to the CH2 and CH3 domains of human IgG1 have been evaluated for their ability to protect against neutrophil-dependent lung injury in rats after systemic activation of C caused by vascular infusion of cobra venom factor (CVF) or lung injury that follows intrapulmonary deposition of IgG immune complexes. Previous studies using anti-selectin antibodies have suggested that the former model is P-selectin dependent, whereas the latter is E-selectin dependent. Requirements for L-selectin have not been identified because of lack of reagents. For the current studies employing the CVF model of lung injury, infusion of P-selectin-Ig chimera reduced injury (as assessed by changes in permeability and hemorrhage) in a dose-dependent manner, with parallel reductions in lung myeloperoxidase (MPO) content. Similar results were obtained with the L-selectin-Ig chimera, whereas the E-selectin-Ig chimera was not protective and failed to alter MPO content. In contrast, in the IgG immune complex model of lung injury, the L- and E-selectin-Ig chimeras both showed dose-related protective effects and reductions in MPO content, whereas the P-selectin-Ig chimera failed to protect against injury and did not alter MPO content in this model of lung injury. In all cases of blocking of injury, this was incomplete, suggesting multi-selectin engagement or inadequate amounts of selectin-Ig chimeras employed. These data indicate that neutrophil recruitment and attendant lung injury in the CVF model are L- and P-selectin dependent and E-selectin-independent, whereas in the IgG immune complex model, neutrophil recruitment and lung injury are L- and E-selectin-dependent but independent of P-selectin. Thus, differing selectin requirements for acute inflammatory lung injury have been identified.
...
PMID:Protective effects of selectin chimeras in neutrophil-mediated lung injury. 750 20

The objective of this study was to determine whether pulmonary endothelial expression of the adhesive glycoprotein P-selectin contributes to the lung injury and leukostasis observed after intestinal ischemia-reperfusion (I/R). The pulmonary capillary filtration coefficient and lung myeloperoxidase activity were determined in rat lungs isolated after 120 min of superior mesenteric artery occlusion and 90 min of reperfusion. Intestinal I/R resulted in a marked increase in the pulmonary capillary filtration coefficient compared with control and sham-operated rats. The increase in pulmonary microvascular permeability elicited by intestinal I/R was effectively prevented by pretreatment with a P-selectin monoclonal antibody (MAb; MAb PB1.3) but was unaffected by a control MAb. The intestinal I/R-induced increase in pulmonary microvascular permeability was accompanied by a dramatic sequestration of granulocytes in the lung compared with control and sham-operated rats; however, neither the P-selectin nor the control MAbs affected this event. These results indicate that P-selectin contributes to the pulmonary microvascular dysfunction observed after intestinal I/R. The inhibition of intestinal I/R-induced lung injury by immunoneutralization of P-selectin appears to be unrelated to the accompanying lung leukosequestration.
...
PMID:Pulmonary microvascular injury after intestinal ischemia-reperfusion: role of P-selectin. 751 Feb 79

Ischemia (4-hour) followed by reperfusion (4-hour) of rat hind limbs results in local injury as well as remote (lung) injury. It has recently been shown that injury in this model is neutrophil- and cytokine-dependent and requires the beta 2 integrin adhesion molecules CD11a/CD18 and CD11b/CD18. The role of selectins in events leading to injury (as determined by leakage of albumin and by hemorrhage) was assessed either through the use of blocking antibodies to L-, E- or P-selectins or by the use of oligosaccharides that are reactive with selectins. Lung injury was found to be L- and E-selectin-dependent. When the ischemia and reperfusion times were reduced, lung injury was also found to be P-selectin dependent. In the case of hind limb injury involving the crural muscle mass, injury was L-selectin-dependent but independent of requirements for P- and E-selectin. Injury in both organs was blocked by the infusion of sialylated Lewis pentasaccharide, whereas sialyl-N-acetyllactosamine pentasaccharide failed to protect against injury. In general, when selectin-blocking approaches were protective, there were parallel reductions in tissue content of myeloperoxidase. These data underscore the role of selectins in ischemia-reperfusion injury and suggest that selectin requirements may vary with the vascular bed under study.
...
PMID:Role of selectins in local and remote tissue injury following ischemia and reperfusion. 751 Apr 57

Acute second degree thermal injury of rat skin involving 25 to 30% total body surface of anesthetized rats results at 4 hours in evidence of vascular injury both locally (in skin) and remotely (involving lung). The neutrophil dependency for both types of injury has now been established. Monoclonal antibodies to various adhesion molecules have been used to define the requirements for these molecules in the development of vascular injury. In dermal vascular injury, a requirement for Mac-1 (CD11b/CD18) but not for leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18) has been established. In this model requirements have also been demonstrated for intercellular adhesion molecule-1 (ICAM-1) and E- and L-selectin but not for very late arising antigen-4 (VLA-4) or P-selectin. With respect to lung vascular injury, dual requirements for both leukocyte function-associated antigen-1 and Mac-1 were found as well as for ICAM-1 and E- and L-selectin but not for VLA-4 and P-selectin. In the lung, there was a close correlation between neutrophil content of the tissue (as assessed by myeloperoxidase) and the effects of protective interventions (directed against blocking of adhesion molecules). These data emphasize the roles of beta 2 integrins, selectins (L and E), and ICAM-1 in events that lead to neutrophil-mediated vascular injury of dermis and lung after thermal trauma to skin.
...
PMID:Role of leukocyte adhesion molecules in lung and dermal vascular injury after thermal trauma of skin. 751 48

Plasma concentrations of lactoferrin relevant to an inflammatory response are known to elicit leukocyte-endothelial cell adhesion in mesenteric venules. The objectives of this study were (1) to determine whether exogenously administered lactoferrin causes microvascular and mucosal injury in rat intestine and (2) to assess the contribution of adherent leukocytes to a lactoferrin-mediated injury process. Mucosal myeloperoxidase (MPO) activity and vascular protein clearance were monitored in the distal intestine of male Sprague-Dawley rats. Macroscopic erosive lesions of the mucosa and increases in mucosal MPO and intestinal vascular protein were observed 2 h following the lactoferrin infusion, results consistent with granulocyte accumulation and microvascular protein leakage. These lactoferrin-induced alterations were significantly attenuated in animals pretreated with a monoclonal antibody (mAb) directed against P-selectin but not by an E-selectin-specific mAb. In another series of experiments, leukocyte adherence/emigration and leakage of fluorescein isothiocyanate (FITC)-labeled albumin were measured in rat mesenteric venules using intravital video microscopy. Lactoferrin elicited increases in both leukocyte adhesion/emigration and albumin extravasation, which were attenuated by mAbs directed against P-selectin but not E-selectin. These observations indicate that (1) the lactoferrin released by activated neutrophils may lead to significant microvascular and mucosal injury or dysfunction and (2) the lactoferrin-induced injury is related to P-selectin-mediated adhesion of leukocytes to microvascular endothelium. Our results raise the possibility that neutrophil-derived lactoferrin contributes to the inflammatory response by promoting further granulocyte accumulation and activation and that mAbs to P-selectin may be therapeutically beneficial in inflammatory disorders.
...
PMID:P-selectin-dependent leukocyte recruitment and intestinal mucosal injury induced by lactoferrin. 751 95

The role of P-selectin in leukocyte-endothelial interaction after splanchnic arterial occlusion and reperfusion (SAO/R) in pentobarbital-anesthetized rats was investigated employing a P-selectin-neutralizing monoclonal antibody (i.e., MAb PB1.3). MAb PB1.3 (1 mg/kg) given intravenously to SAO/R rats just before reperfusion significantly attenuated leukocyte rolling and adherence in mesenteric postcapillary venules as observed via intravital microscopy. Likewise, ileal myeloperoxidase (MPO) activity was decreased from 4.6 +/- 0.6 in nontreated ischemic rats to 2.0 +/- 0.2 U/100 mg (P < 0.01), indicating a lesser degree of polymorphonuclear leukocyte (PMN) accumulation. A significantly lower plasma free amino-nitrogen concentration was observed in MAb PB1.3-treated rats vs. untreated (P < 0.01), suggesting decreased tissue injury after reperfusion. Immunohistochemical localization demonstrated significant expression of P-selectin in endothelial cells lining ileal postcapillary venules 30 min after reperfusion of the ischemic splanchnic circulation. Thus P-selectin appears to plays an important role in leukocyte accumulation after splanchnic ischemia-reperfusion, and the MAb PB1.3 attenuates the accumulation of PMNs in the ischemic-reperfused small bowel, resulting in reduced tissue injury.
...
PMID:Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion. 752 Jun 70

N,N,N-trimethylsphingosine (TMS), a stable synthetic sphingosine derivative, was investigated in a feline model of myocardial ischemia (90 min) and reperfusion (270 min) injury. TMS (60 micrograms/kg), administered intravenously 10 min before reperfusion, significantly attenuated myocardial necrosis (15 +/- 3 vs. 31 +/- 4% necrosis of area at risk, P < 0.01) and cardiac myeloperoxidase activities, a marker of neutrophil accumulation, compared with vehicle-treated cats. Endothelium-dependent relaxation to acetylcholine in ischemic-reperfused coronary artery rings treated with TMS was also significantly preserved compared with vehicle (73 +/- 4 vs. 34 +/- 4% vasorelaxation, P < 0.01). Polymorphonuclear neutrophil (PMN) adherence to coronary endothelium 270 min after reperfusion was markedly attenuated in the TMS group compared with vehicle-treated cats (37 +/- 5 vs. 76 +/- 5 PMN/mm2, P < 0.01). TMS also attenuated upregulation of P-selectin on coronary venular endothelium by immunohistochemistry. This was consistent with in vitro findings that TMS attenuates PMN adherence to thrombin-stimulated coronary endothelium and P-selectin upregulation on thrombin-stimulated cat platelets. A sphingolipid derivative, TMS at physiological concentrations exerts cardioprotective actions and preserves coronary endothelial function following myocardial ischemia and reperfusion in vivo. The effects appear to be mediated by the inhibition of PMN-endothelial interaction and subsequent accumulation into the ischemic myocardium. Thus TMS may be a useful agent in attenuating myocardial reperfusion injury.
...
PMID:Myocardial and endothelial protection by TMS in ischemia-reperfusion injury. 754 41

Neutrophil adherence and/or aggregation has been implicated in ischemia reperfusion injuries. We examined the role of P-selectin in PMN-mediated injury after reperfusion of the rabbit ear. The ear was partially amputated, and then reattached leaving the central artery and vein intact. To induce ischemia the central artery was then occluded. Treatment was at reperfusion with either saline or one of two murine P-selectin mAbs, designated PB1.3 and PNB1.6 mAb PB1.3 cross-reacts with rabbit P-selectin and prevents histamine-induced leukocyte rolling, whereas PNB1.6 does not. Using a peroxidase-antiperoxidase system P-selectin was detected in the ischemic ear, but not in the nonischemic ear. Ear volume increased to 5.3 times baseline in the saline-treated animals (n = 8), 6.6 times baseline in the nonblocking mAb PNB1.6-treated animals (n = 2), and 3.7 times baseline in the blocking mAb PB1.3-treated animals (n = 8). Estimated tissue necrosis of the combined saline- and PNB1.6-treated animals was 46 vs. 2.7% for the mAb PB1.3-treated animals. We conclude that: (a) P-selectin is expressed in ischemia reperfusion; (b) P-selectin participates in PMN-endothelial cell interactions in ischemia reperfusion; and (c) inhibiting P-selectin adhesion significantly reduces reperfusion injury.
...
PMID:Anti-P-selectin monoclonal antibody attenuates reperfusion injury to the rabbit ear. 769 90

Endothelial-monocyte activating polypeptide II (EMAP II) was initially identified in the supernatant of murine methylcholanthrene A-induced fibrosarcomas (Meth A) by its capacity to activate host effector cells (Kao, J., Ryan, J., Brett, J., Chen, J., Shen, H., Fan, Y-G., Godman, G., Familletti, P., Wang, F., Pan, Y-C., Stern, D., and Clauss, M. (1992) J. Biol. Chem. 267, 20239-20247). Based on the NH2-terminal protein sequence, a full-length cDNA has been cloned which indicates that the precursor of EMAP II is a unique, leaderless, single polypeptide chain with predicted molecular mass approximately 34 kDa and that the mature form released by Meth A cells corresponds to approximately 20 kDa. Purified recombinant mature EMAP II (EMAP II, approximately 20 kDa form) activated endothelial cells with resulting elevation of cytosolic free calcium concentration, release of von Willebrand factor, induction of tissue factor, and expression of the adhesion molecules E-selectin and P-selectin. Neutrophils exposed to EMAP II demonstrated elevated cytosolic free calcium concentration, peroxidase generation, and chemotaxis. EMAP II also activated mononuclear phagocytes elevating cytosolic free calcium concentration, inducing tumor necrosis factor-alpha (TNF) and tissue factor, and stimulating chemotaxis. Systemic infusion of EMAP II into C3H/HeJ or Balb/c mice was associated with systemic toxicity, pulmonary congestion, and the appearance of TNF, interleukin-1 and -6 in the plasma. A single intra-tumor injection of EMAP II into Meth A sarcomas induced acute thrombohemorrhage and partial tumor regression. Local injection of EMAP II into a tumor resistant to the effects of TNF, murine mammary carcinoma, rendered it sensitive to subsequently administered TNF, which resulted in acute thrombohemorrhage and partial regression. These data suggest that recombinant EMAP II, a tumor-derived cytokine, has properties of a proinflammatory mediator with the capacity to prime the tumor vasculature for a locally destructive process.
...
PMID:Characterization of a novel tumor-derived cytokine. Endothelial-monocyte activating polypeptide II. 792 99


1 2 3 4 5 6 7 8 9 10 Next >>

---