Role of platelet-activating factor in leukocyte-independent plasma extravasation and mast cell activation during endotoxemia

Background. Independently from leukocyte adherence, endothelial factors and mast cell activation seems to promote microvascular permeability. Platelet -activating factor (PAF) has been shown to play a significant role in endot oxin-induced leukocyte adherence. The aim of our study was to investigate i f there is also a role for PAF in mediating leukocyte-independent microvasc ular permeability changes and activation of mast cells during endotoxemia. Therefore, during endotoxemia microvascular permeability and mast cell acti vation were determined after inhibition of L-selectin-mediated leukocyte ad herence by fucoidin and after inhibition of PAF effects by the PAF receptor antagonist BN52021, Materials and methods, In male Wistar rats, red cell velocity (V-RBC) venul ar wall shear rate, microvascular permeability, leukocyte adherence, and ma st cell activation were determined in mesenteric postcapillary venules usin g intravital microscopy at baseline and 60 and 120 min after start of a con tinuous infusion of endotoxin (ETX; 2 mg/kg/h, Escherichia coli O26:B6) (ET X group). Animals in the FUCO/ETX group received fucoidin (25 mg/kg body wt ) in addition to the procedure described above, Animals in the FUCO/ETX/ PA F-ANT group received fucoidin and the PAF receptor antagonist BN52021 (5 mg /kg body wt) prior to the continuous endotoxin infusion. Control animals (c ontrol group) received only equivalent volumes of Nacl 0.9%, Results. There were no microhemodynamic and macrohemodynamic differences be tween groups, In. all endotoxin-challenged groups macromolecular leakage an d mast cell activity increased significantly, starting at 60 min. Both macr omolecular leakage and mast cell activity were significantly higher in the FUCO/ETX group than in the FUCO/ETX/PAF-ANT group and control group. Differ ences in macromolecular leakage between groups were significant at 120 min. Differences in mast cell activity between groups were significant at 60 an d 120 min. Conclusions. The results of our study demonstrate a leukocyte-independent p lasma extravasation that can be inhibited by the PAF receptor antagonist BN 52021, indicating the involvement of PAF in the pathophysiology of leukocyt e-independent microvascular damage during early endotoxemia, Mast cell acti vity seems to precede leukocyte-independent macromolecular leakage. (C) 200 0 Academic Press.