Platelet-activating factor causes neutrophil accumulation and neutrophil-mediated increased vascular permeability in...

Platelet-activating factor (PAF) has potent effects on the respiratory airways that may be mediated through its ability to act as an inflammatory stimulant. To study its inflammatory properties in the airways, we infused PAF into the vasculature of the canine trachea and examined (1) the kinetics of neutrophil transit through the tracheal microcirculation, (2) accompanying changes in vascular permeability, and (3) the dependence of vascular permeability changes on neutrophil accumulation. Neutrophil kinetics were assessed by measuring the transit times of fluorescein isothiocyanate-labeled canine neutrophils by in vivo microscopy. Changes in vascular permeability were measured by the extravascular leakage of radiolabeled albumin and comparison of wet-to-dry weight ratios. The importance of neutrophils in increasing vascular permeability was assessed by perfusing the trachea with either autologous blood depleted of its leukocytes, or leukocyte-depleted blood replenished with neutrophils. Our data indicate that PAF causes rapid and prolonged neutrophil accumulation in the canine trachea and an increase in vascular permeability that is partially mediated by neutrophils.