Immune-complex-induced inflammatory reaction studied by intravital microscopy: role of histamine and arachidonic acid metabolites.

An immune-complex-induced inflammatory reaction was elicited in the hamster cheek pouch microvasculature of ovalbumin (OA)-immunized animals by exposure to 1 or 100 micrograms/ml OA. The low antigen dose caused arteriolar constriction, transient platelet aggregation, and a reversible increase in vascular leakage at postcapillary venules. With the high antigen dose, the constriction and platelet aggregation were more pronounced and the vascular leakage was prolonged. This antigen dose also caused a massive PMNL accumulation in small venules, which coincided with the prolonged vascular leakage. Histamine was released in the reaction as pretreatment with mepyramine largely inhibited the leakage response to 1 microgram/ml OA. With 100 micrograms/ml OA, only the initial phase of vascular leakage was inhibited by mepyramine, leaving the prolonged vascular leakage and PMNL accumulation unaltered. Pretreatment with methylprednisolone 16-18 h prior to the experiments reduced both phases of vascular leakage as well as the PMNL accumulation. Pretreatment with the combined cyclo- and lipoxygenase inhibitors BW755C or nordihydroguaiaretic acid (NDGA) reduced the initial vasoconstriction induced with 100 micrograms/ml OA, thereby augmenting the initial vascular leakage. Despite this, the prolonged phase of vascular leakage was reduced in the NDGA-treated animals. Cyclooxygenase products were not found to play a crucial role in mediating the vascular response; on the contrary, indomethacin pretreatment slightly potentiated the vascular leakage induced by the low antigen dose.