DIFFERENTIAL INHIBITION OF POLYMORPHONUCLEAR LEUKOCYTE RECRUITMENT IN-VIVO BY DEXTRAN SULFATE AND FUCOIDAN

THE selectin-mediated rolling of leukocytes along the endothelial cell s is a prerequisite step followed by firm adhesion and extravasation i nto the inflamed tissue, This initial contact can be suppressed by sul phated polysaccharides. We have studied the effect of sulphated polysa ccharides on the ultimate polymorphonuclear leukocyte (PMN) recruitmen t and plasma leakage in rabbit skin in response to intradermal injecti on of various inflammatory mediators. PMN infiltration evoked by vario us PMN chemoattractants (FMLP, C5a desArg, LTB(4) and IL-8) was signif icantly inhibited after intra venous injection of dextran sulphate (25 mg/kg), heparin (2 x 90 mg/kg) or fucoidan (1 mg/kg), PMN-dependent p lasma leakage was equally well reduced by the different sulphated poly mers. Vascular permeability induced by histamine or thrombin acting vi a a PMN-independent mechanism was not reduced, Fucoidan was the only p olysaccharide able to suppress IL-l-induced PMN infiltration for 60-70 %. Local administration of dextran sulphate had no effect on PMN-depen dent plasma leakage, Differential inhibition of PMN recruitment was de termined after injection of dextran sulphate or fucoidan depending on the type of insult. Therefore, these results suggest that different ad hesion pathways are utilized during PMN recruitment in vivo in respons e to chemoattractants and IL-1.