Oxygen free radicals and leukotriene B4 induced increase in vascular leakage is mediated by polymorphonuclear...

Topical application of the arachidonic acid metabolite leukotriene B4 (LTB4), known to be a potent chemotactic and chemokinetic substance or the superoxide radical producing enzyme xanthine oxidase (XO) initiate an increase in adhering polymorphonuclear leukocytes (PMN) along the venular endothelium and an increase in vascular leakage of fluorescein labelled dextran (Mw 150.000) in the hamster cheek pouch microvasculature. We have studied the contribution of PMN in the permeability response induced with LTB4 or XO. Animals made neutropenic by pretreatment with antineutrophil serum (ANS) obtained from immunized rabbits, showed a dramatically decreased leakage response to LTB4 or XO, whereas the response to histamine was unaffected. These results suggest that LTB4 and XO induced increase in vascular leakage is mediated by PMN adhering to the venular endothelium. Extensions can be made to acute inflammatory responses characterized by accumulation of PMN, vascular leakage and oedema formation.