Modulation of PAF-induced leukocyte adherence and increased microvascular permeability

The objective of this study was to assess whether superoxide and leukocyte adhesion glycoproteins (CD18) mediate the leukocyte adherence to mesenteric microvessels and increased intestinal microvascular permeability induced by platelet-activating factor (PAF). PAF was infused into the arterial supply of an isolated autoperfused segment of cat intestine. Thirty minutes into the infusion, the number of adherent leukocytes within mesenteric venules was measured. This was followed by intravenous administration of either human recombinant superoxide dismutase (hSOD), hydrogen peroxide-inactivated hSOD, or a monoclonal antibody against the leukocyte adhesion molecule CD18 (MoAb IB4), and 30 min later, adherence measurements were repeated. hSOD and MoAb IB4 produced a 30 and 66% decrease, respectively, in leukocyte adherence, whereas inactivated hSOD had no effect. Adherence of PAF-activated cat neutrophils to plastic was reduced only by MoAb IB4, suggesting that PAF-induced leukocyte adherence is mediated by both CD18 and superoxide and that endothelium is necessary for the superoxide-mediated adhesion. In a correlate study, hSOD and MoAb IB4 were shown to attenuate the PAF-induced increase in microvascular permeability by 40 and 70%, respectively. These data indicate that the increased microvascular permeability induced by PAF can be attenuated when leukocyte adherence to microvascular endothelium is reduced using molecules that either bind to CD18 adhesive glycoproteins or scavenge superoxide.