Platelet-activating factor modulates leukocyte adhesion to endothelium in ischemia-reperfusion.

Platelet-activating factor (PAF) is an important proinflammatory phospholipid that may be involved in modulating leukocyte-endothelium (L-E) adhesion in ischemia-reperfusion (I-R). We investigated the role of PAF receptors in postischemic reperfusion using our model of I-R in the hamster cheek pouch microcirculation. The model allows for measurements of ischemic and nonischemic areas in the same preparation. We assessed the increase in the number of adhering leukocytes (per 100-microns vessel length) as an index of I-R-induced microvascular dysfunction. To test the influence of endogenous PAF, we administered WEB 2086 (2 mg/kg iv), a PAF receptor inhibitor. In the control I-R group (Group 1), the number of adhering leukocytes (mean +/- SEM) increased from 3.3 +/- 0.7 at baseline to 9.5 +/- 1.0 at the end of 1 hr of reperfusion. In a second group of animals (Group 2) receiving WEB 2086 prior to ischemia, there was no significant difference between the preischemic baseline and the values recorded after 1 hr of reperfusion (3.5 +/- 0.5 vs 3.8 +/- 0.5). In a third group of hamsters (Group 3) receiving WEB 2086 10 min prior to reperfusion, there was no significant difference between the baseline values and those at 1 hr of reperfusion (2.3 +/- 0.3 vs 2.3 +/- 0.2). Similarly, in Groups 2 and 3, with WEB 2086 treatment, there was no significant difference between the values measured in the ischemic areas and their time-matched nonischemic areas at the end of 1 hr of reperfusion (Group 2, 3.8 +/- 0.5 vs 3.0 +/- 0.4; Group 3, 2.3 +/- 0.2 vs 3.2 +/- 0.4). Our data demonstrate (1) an important role for PAF receptors in modulating L-E adhesion in I-R and (2) that blockade of PAF receptors either prior to ischemia or prior to reperfusion reduces adhesion of leukocytes to endothelium. Our results suggest that PAF receptor blockade in postischemic tissues could be a new therapeutic approach to decrease the impact of ischemia-reperfusion injury.