HISTAMINE CAN INDUCE LEUKOCYTE ROLLING IN RAT MESENTERIC VENULES

Rolling is a retarded movement of leukocytes that depends on the function of the selectin class of adhesion molecules. In venules of internal organs, rolling is rapidly induced on tissue exposure by unknown mediator(s). Rolling was investigated with intravital microscopy in venules of the exteriorized mesentery of anesthetized rats. Immediately after exteriorization, rolling leukocyte flux was very low (10 +/- 4 min(-1)) and increased rapidly to reach a peak of 76 +/- 10 min(-1) at 30 min. Intraperitoneal pretreatment of rats with histamine induced near-maximal rolling in mesenteric venules immediately after exteriorization. Leukocyte rolling was significantly inhibited by intravenular microinfusion of monoclonal antibody PB1.3 that recognizes and functionally blocks human and rat P-selectin. The effect of histamine was blocked by pretreatment with ranitidine, an Hz-receptor antagonist, but not with diphenhydramine, which blocks H-1 receptors. However, ranitidine did not block the subsequent increase of rolling leukocyte flux, and rolling leukocyte flux was similar in all groups 20 min after exteriorization. Histological investigation revealed degranulation of mast cells, suggesting release of histamine and other mediators. These findings indicate that histamine can induce leukocyte rolling in vivo via H-2 receptors, most likely by inducing endothelial expression of P-selectin. In addition, mediators other than histamine released from mast cells and/or other cells are likely to promote sustained rolling.