PLATELET-ACTIVATING-FACTOR MODULATES LEUKOCYTE ADHESION TO ENDOTHELIUM IN ISCHEMIA-REPERFUSION

Platelet-activating factor (PAF) is an important proinflammatory phosp holipid that may be involved in modulating leukocyte-endothelium (L-E) adhesion in ischemia-reperfusion (I-R). We investigated the role of P AF receptors in postischemic reperfusion using our model of I-R in the hamster cheek pouch microcirculation. The model allows for measuremen ts of ischemic and nonischemic areas in the same preparation. We asses sed the increase in the number of adhering leukocytes (per 100-mu m ve ssel length) as an index of I-R-induced microvascular dysfunction. To test the influence of endogenous PAF, we administered WEB 2086 (2 mg/k g iv), a PAF receptor inhibitor. In the control I-R group (Group 1), t he 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. Ln a second group of animals (Group 2) receiving WEB 2086 prior to ischem ia, there was no significant difference between the preischemic baseli ne 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 betw een 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 t he 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 rol e for PAF receptors in modulating L-E adhesion in I-R and (2) that blo ckade of PAF receptors either prior to ischemia or prior to reperfusio n reduces adhesion of leukocytes to endothelium. Our results suggest t hat PAF receptor blockade in postischemic tissues could be a new thera peutic approach to decrease the impact of ischemia-reperfusion injury. (C) 1996 Academic Press, Inc.