Effect of early transient adherent leukocytes on venular permeability and endothelial actin cytoskeleton

Abstract

In a time course study of the development and recovery of venular leaks, it was shown that, after as early as 3 min of histamine application, venular leak formation was identified [Baldwin, A. L., and G. Thurston. Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H1528-H1537, 1995]. This was accompanied by changes in the endothelial actin cytoskeleton and the presence of adherent leukocytes. The venular leaks remained elevated for at least 30 min, whereas the adherent leukocytes were decreased by 20 min. The present study was performed to determine the role that 3 min (early), transient histamine-associated adherent leukocytes play in the formation of venular leaks and changes in the endothelial actin cytoskeleton. In anesthetized rats, the microvasculature of a mesenteric window was perfused with buffered saline or fucoidin. FITC-BSA or FITC-BSA and 10-4 M histamine was added to the perfusate for the last 3 min. The vasculature was perfusion fixed, stained for filamentous actin, and viewed microscopically. Fucoidin pretreatment significantly reduced the number of early, transient histamine- associated adherent leukocytes (P < 0.01). The number of adherent leukocytes in leaky venules was significantly greater than that seen in nonleaky venules (P < 0.01); however, the reduction in the number of histamine-associated adherent leukocytes with fucoidin pretreatment had no significant effect on the number (P > 0.05) or area (P > 0.05) of FITC-BSA leaks or on the endothelial actin cytoskeleton.