Thrombin-Treated Endothelium Primes Neutrophil Functions: Inhibition by Platelet-Activating Factor Receptor Antagonists

Vercellotti, G. M.; Wickham, Nicholas; Gustafson, K. S.; Yin, HQ; Hebert, M.; Jacob, Harry S.

doi:10.1002/jlb.45.6.483

Cited by 41 publications

(12 citation statements)

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“…In this case, mAb 60.3 binds to a function-related idiotype of CD18 (23) OF-due to CD18-mediated adhesion without having used an antibody to a nonfunctional neutrophil surface epitope. Platelets may also be involved in this injury in a mutually amplifying process involving platelet activation by neutrophilinjured endothelium and by platelet-activating factor priming of neutrophils (24).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of leukocyte adherence by anti-CD18 monoclonal antibody attenuates reperfusion injury in the rabbit ear.

Vedder

Winn

Rice

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

166

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Tissue injury resulting from ischemia and reperfusion forms the basis of several important disorders including myocardial infarction, stroke, and circulatory shock. To examine the role of neutrophils in this process and to determine the extent to which injury is a consequence of reperfusion, we utilized the monoclonal antibody 60.3, directed to CD18, the human leukocyte adherence glycoprotein, to block intravascular neutrophil aggregation and neutrophil adherence to endothelium in a rabbit model of tissue ischemia and reperfusion. Antibody treatment either before ischemia or after ischemia, but prior to reperfusion, resulted in the same degree of significant protection against endothelial, microvascular, and tissue injury. We conclude that neutrophils and increased neutrophil adhesiveness are important in the development of microvascular and tissue injury after ischemia and reperfusion and that under these circumstances, injury is primarily a consequence of reperfusion.Ischemia-related cellular, tissue, and organ injury form the basis of many important clinical disorders, including myocardial infarction, stroke, vascular disease, organ transplantation, and circulatory shock. Much progress has been made in the area of early restoration or perfusion. However, there is evidence that under certain circumstances, a significant proportion of the injury associated with ischemia may be a consequence of events associated with reperfusion of ischemic tissues, i.e., "reperfusion injury" (1, 2). This concept has clinical implications since specific therapy usually cannot be instituted until after the ischemic event, whereas it may be feasible to administer therapy prior to reperfusion.Oxygen-derived free radicals, generated within the tissues at the time of reperfusion, have been identified as potentially important mediators of this reperfusion injury (3). Another important source of free radicals is the neutrophil. Activated neutrophils can also release proteases and phospholipase products, all of which are capable of causing significant cellular and tissue injury (4, 5). Neutrophil-mediated endothelial injury has been demonstrated to result in loss of vascular integrity, edema, hemorrhage, thrombosis, and tissue necrosis. An important role for neutrophils in ischemiareperfusion injury is suggested by studies that have shown a close association between neutrophil accumulation and tissue injury in this setting (6) and by studies that have demonstrated significant injury reduction by depletion of circulating neutrophils (7,8).Increased neutrophil adhesiveness is a critical early step in the sequence of events leading to neutrophil-mediated injury (4). An alternative approach to the investigation and perhaps to therapy of neutrophil-mediated injury has developed from studies that have identified a human neutrophil membrane glycoprotein heterodimer, designated CD11b/CD18 (Mac-i, Mol), which plays a major role in mediating neutrophil adhesiveness (9). We have shown that specific monoclonal antibodies (mAbs) directed to ...

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Section: Discussionmentioning

confidence: 99%

Inhibition of leukocyte adherence by anti-CD18 monoclonal antibody attenuates reperfusion injury in the rabbit ear.

Vedder

Winn

Rice

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

166

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“…Several chemotactic and activating trol group, and accumulation of PMNs in the sinusoids factors are reported to modulate the process, including anawas more obvious and prolonged in the former. ICAM-1 phylatoxin C5a, 17 N-formyl-methionyl peptides, 18 leukotriene expression was enhanced in both groups with a peak B 4 , 19 platelet-activating factor, 20 and interleukin (IL)-8. 5,21 In between 24 and 48 hours after partial hepatectomy.…”

Section: -12 It Is Well Known That Phosphorylase (Pnp)/alanine Tranmentioning

confidence: 99%

Neutrophil–Mediated Sinusoidal Endothelial Cell Injury After Extensive Hepatectomy in Cholestatic Rats

et al. 1997

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ative hepatic failure in such cases is still poorly understood, The aim of this study was to assess the hypothesis that we have previously noticed appreciable accumulations of hepatic failure after extensive hepatectomy in patients polymorphonuclear neutrophils (PMNs) in the liver at auwith obstructive jaundice (OJ) may be mediated by polytopsy. 3 Aside from the cardinal role of PMNs in the host morphonuclear neutrophils (PMN). In the OJ group, rats defense, it has been shown that activated PMNs are impliunderwent a partial hepatectomy of 78% after 2 weeks cated in several serious disorders, such as adult respiratory of cholestasis and subsequent external biliary drainage distress syndrome, rheumatoid arthritis, myocardial reperfufor 5 days. In the sham-operated control group, rats were sion injury, inflammatory bowel disease, 4,5 and idiopathic partially hepatectomized 19 days after the sham surgery. pulmonary fibrosis. 6 These conditions are characterized hisThe concentration of the serum cytokine-induced neutologically by the remarkable accumulation of PMNs at the trophil chemoattractant (CINC), which is homologous injured tissue site. Additionally in liver diseases, infiltration with the growth-related oncogene (gro) product, a memof PMNs can be seen in alcoholic hepatitis 7,8 and reperfusion ber of the human interleukin (IL)-8 family, and a major injury. 9 Recently, the importance of vascular endothelial cell neutrophil chemotactic factor in rats, increased concominjury has been established in these types of organ damage. itantly with accumulation of PMNs in the hepatic sinuSome investigators have reported that the injury of sinusoisoids during cholestasis and subsequent external draindal endothelial cells (SECs) plays an important role in the age. However, changes in the serum purine nucleoside development of hepatic damage. [10][11][12] It is well known that phosphorylase (PNP)/alanine transaminase (ALT) ratioPMNs have the capacity to injure vascular endothelial cells as a marker of sinusoidal endothelial cell (SEC) injury and are one of the most important effector cells for endotheshowed no significant differences between the two lial injury. [13][14][15][16] These findings suggest that PMNs may medigroups. Intercellular adhesion molecule-1 (ICAM-1) exate SEC injury with severe hepatic damage after extensive pression on SECs was not affected by cholestasis and hepatectomy in patients with OJ as well. external drainage. After partial hepatectomy, the serumThe process of PMN-mediated endothelial cell injury in-CINC concentration immediately elevated more promicludes accumulation of PMNs at the target site and their nently in the OJ group than in the sham-operated conpriming and activation. Several chemotactic and activating trol group, and accumulation of PMNs in the sinusoids factors are reported to modulate the process, including anawas more obvious and prolonged in the former. ICAM-1 phylatoxin C5a, 17 N-formyl-methionyl peptides, 18 leukotriene expression was enhanced in both groups with a peak B 4 ,...

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“…16,14 It is not released from the stimulated EC even in the presence of "acceptor" molecules to which it binds, such as albumin. 1,[6][7][8]25,26 Retention of the molecule by EC is consistent with its amphipathic structure, which predicts that it will preferentially associate with cell membranes or appropriate "carriers," such as lipoproteins or transport proteins. The retention of newly synthesized PAF by activated EC prompted studies of the potential biologic roles of cellassociated PAF.…”

Section: Platelet-activating Factor Function In Thrombin-activated Enmentioning

confidence: 80%

“…Others have reported evidence confirming that PAF expressed by EC activated with thrombin can mediate interactions with PMNs. 7,31,32 When expressed on the surface of histamine-or thrombin-activated EC, PAF acts in concert with granule membrane protein-140 (GMP-140, also called PADGEM protein and CD62), a glycoprotein that is constitutively present in secretory granules of EC. GMP-140 is coexpressed with PAF on the plasma membrane of EC acti vated with thrombin or histamine and tethers the PMN to the EC.…”

Section: Fig 3 Blocking the Neutrophil Platelet-activating Factor (mentioning

confidence: 99%

“…This was first clearly shown in endothelial cells 1,6 and has been confirmed in subsequent reports. 7,8 In EC, a part of the newly synthesized PAF is translocated to the plasma membrane. 9 PAF can function as a mediator of juxtacrine intercellular interactions when associated with the plasma membranes of activated cells, 9 as well as when in the fluid phase (see later).…”

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confidence: 99%

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Regulation of Platelet-Activating Factor (PAF) Synthesis and PAF-Mediated Neutrophil Adhesion to Endothelial Cells Activated by Thrombin

Carveth

Shaddy

Whatley

et al. 1992

Semin Thromb Hemost

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Thrombin-Treated Endothelium Primes Neutrophil Functions: Inhibition by Platelet-Activating Factor Receptor Antagonists

Cited by 41 publications

References 0 publications

Inhibition of leukocyte adherence by anti-CD18 monoclonal antibody attenuates reperfusion injury in the rabbit ear.

Inhibition of leukocyte adherence by anti-CD18 monoclonal antibody attenuates reperfusion injury in the rabbit ear.

Neutrophil–Mediated Sinusoidal Endothelial Cell Injury After Extensive Hepatectomy in Cholestatic Rats

Regulation of Platelet-Activating Factor (PAF) Synthesis and PAF-Mediated Neutrophil Adhesion to Endothelial Cells Activated by Thrombin

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