Role of platelet-activating factor in ischemia/reperfusion-induced leukocyte adherence

Kubes, Paul; Ibbotson, Geoffrey C.; Russell, Janice; Wallace, John L.; Granger, D. Neil

doi:10.1152/ajpgi.1990.259.2.g300

Cited by 134 publications

(104 citation statements)

References 18 publications

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“…Indeed, certain effects of endothelin-1 can be attenuated by PAF receptor antagonists (Lagente et al, 1989;Takayashu et al, 1989;Terashita et al, 1989;Battistini et al, 1990;Filep et al, 1991), and endothelin-1-induced PAF synthesis has also been reported (Lopez-Farre et al, 1990 (Voelkel et al, 1986). It is also possible that the bioavailability of these antagonists is different (Kubes et al, 1990). Taken together, these findings suggest that PAF may be an important mediator of the action of endothelin-1 on vascular permeability.…”

Section: Discussionmentioning

confidence: 82%

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

Filep¹,

Sirois

Rousseau

et al. 1991

British J Pharmacology

106

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The objectives of the present experiments were to assess the effects of endothelin‐1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet‐activating factor (PAF) in vascular responses to endothelin‐1 and to examine the vascular effects of combined administration of endothelin‐1 and PAF in conscious rats. Intravenous bolus injection of endothelin‐1 (0.1–2 nmol kg−1) resulted in a dose‐dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose‐dependent increase in haematocrit values. Endothelin‐1 (0.1 and 1 nmol kg−1) increased dose‐dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin‐1 treatment. Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg−1, i.v.) or BN 52021 (10 mg kg−1, i.v.) reduced the endothelin‐1 (1 nmol kg−1)‐induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin‐1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin‐1. When low doses of endothelin‐1 (0.1 nmol kg−1) and PAF (0.19 nmol kg−1) were administered simultaneously, enhanced protein extravasation was detected in the upper and lower bronchi, whereas neither endothelin‐1 nor PAF by themselves affected vascular permeability in these tissues. These changes occurred in the absence of significant changes in MABP. Combined administration of higher doses of endothelin‐1 (1 nmol kg−1) and PAF (1.9 nmol kg−1) resulted in marked increases (up to 530%) in protein extravasation in the airways, pancreas, stomach and duodenum. The effect of endothelin‐1 on permeability was not affected by PAF in the spleen, whereas it was completely inhibited by PAF in the kidney. Combined injection of endothelin‐1 and PAF resulted in a slight, but significant increase in MABP. The present findings show that endothelin‐1 is capable of increasing vascular permeability in selected vascular beds including the airways, gastrointestinal tract and kidney, and suggest that PAF may mediate, in part, its action on permeability, but not its hypotensive action. The present data also suggest that endothelin‐1 and PAF can act in concert to increase vascular permeability in rat airways and gastrointestinal tract.

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Section: Discussionmentioning

confidence: 82%

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

Filep¹,

Sirois

Rousseau

et al. 1991

British J Pharmacology

106

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“…Furthermore, activated platelets per se are also a source of reactive oxygen species (18,19). The platelet agonists platelet-activating factor and thrombin are also known to mediate I/R-induced leukocyte adhesion (14,27). Thrombin in particular is a potent activator of platelets leading to increased P-selectin expression (10).…”

Section: Discussionmentioning

confidence: 99%

Time-dependent platelet-vessel wall interactions induced by intestinal ischemia-reperfusion

Cooper

Chitman

Williams

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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roll and adhere in venules exposed to ischemia-reperfusion (I/R). This platelet-endothelial adhesion may influence leukocyte trafficking because platelet depletion decreases I/Rinduced leukocyte emigration. The objectives of this study were 1) to assess the time course of platelet adhesion in the small bowel after I/R and 2) to determine the roles of endothelial and/or platelet P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) in this adhesion. The adhesion of fluorescently labeled platelets was monitored by intravital microscopy in postcapillary venules exposed to 45 min of ischemia and up to 8 h of reperfusion. Peak platelet adhesion was observed at 4 h of reperfusion. To assess the contributions of platelet and endothelial cell P-selectin, platelets from Pselectin-deficient and wild-type mice were infused into wildtype and P-selectin-deficient mice, respectively. Platelets deficient in P-selectin exhibited low levels of adhesion comparable to that in sham-treated animals. In the absence of endothelial P-selectin, platelet adhesion was reduced by 65%. Treatment with a blocking antibody against PSGL-1 reduced adhesion by 57%. These results indicate that I/R induces a time-dependent platelet-endothelial adhesion response in postcapillary venules via a mechanism that involves PSGL-1 and both platelet and endothelial P-selectin, with platelet P-selectin playing a greater role.

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“…In numerous models of inflammation, PAF has been shown to act through its specific receptor on target cells, leading to elevated intracellular calcium levels followed by production of additional mediators and to changes in vascular permeability characteristic of the inflammatory involvement of the tissue. [27][28][29] In general terms, the involvement of the vascular endothelium in inflammatory responses has been carefully and extensively defined. 30 Endothelial cells have been shown to respond to a variety of stimuli leading to the synthesis and expression of regulators critical to recruitment of circulating immune cells to inflamed tissues.…”

Section: Discussionmentioning

confidence: 99%

Localization of the Platelet-Activating Factor Receptor to Rat Pancreatic Microvascular Endothelial Cells

Flickinger

Olson

1999

The American Journal of Pathology

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Platelet-activating factor (PAF) is a potent lipid autocoid involved in numerous inflammatory processes.Although PAF plays a key role as a mediator of inflammation in acute pancreatitis , the site(s) of action of PAF in the pancreas remains unknown. One of the aims of this study was to identify cell types within the pancreas expressing the PAF receptor using immunohistochemical protocols. Additionally , pancreatic microvascular endothelial cells were isolated and examined for the PAF receptor using immunohistochemistry , reverse transcription-polymerase chain reaction , and intracellular calcium responses to PAF exposure. Immunohistochemical analysis of pancreatic slices using an antibody directed toward the N-terminus of the PAF receptor revealed specific localization to the vascular endothelium with no localization to other pancreatic cell types. Reverse transcription-polymerase chain reaction of RNA isolated from cultured pancreatic islet endothelial cells yielded the predicted amplicon for the PAF receptor. Platelet-activating factor (PAF) is a phosphatidylcholine molecule containing a long chain alkyl ether moiety in the sn-1 position that is acetylated at the sn-2 position.1 The biological activity of PAF occurs though its specific receptor, which is a member of the G-protein-coupled receptor superfamily, and leads to the activation of multiple signaling pathways. 2 This unique phospholipid acts to mediate a host of biochemical activities including angiogenesis, inflammation, and reproduction. 3,4

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Role of platelet-activating factor in ischemia/reperfusion-induced leukocyte adherence

Cited by 134 publications

References 18 publications

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

Time-dependent platelet-vessel wall interactions induced by intestinal ischemia-reperfusion

Localization of the Platelet-Activating Factor Receptor to Rat Pancreatic Microvascular Endothelial Cells

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