CYTOKINE-INDUCED LEUKOCYTE ROLLING IN MOUSE CREMASTER MUSCLE ARTERIOLES IS P-SELECTIN DEPENDENT

Leukocyte rolling and adhesion are generally observed in venules but r arely observed in arterioles. With the use of intravital microscopy, w e found that a 4-h treatment with interleukin-1 beta (IL-1 beta) and t umor necrosis factor-alpha (TNF-alpha) dose dependently induced leukoc yte rolling and adhesion in arterioles of the mouse cremaster muscle. The rolling response lasted more than 24 h and was completely inhibite d by treatment with the sulfated polysaccharide fucoidin. Moreover, we found that costimulation with IL-1 beta and TNF-alpha for 4 h synergi stically increased arteriolar leukocyte rolling, i.e., threshold doses of IL-1 beta and TNF-alpha together caused a more than 10-fold increa se of rolling in arterioles compared with the sum of the individual re sponses. This rolling interaction was abolished by treatment with a mo noclonal antibody directed against P-selectin (RB40.34), but it appare ntly was unaffected by a monoclonal antibody against L-selectin (MEL-1 4). Taken together, our functional data show that IL-1 beta and TNF-al pha separately induce and synergistically increase P-selectin-dependen t leukocyte rolling and firm adhesion in mouse cremaster arterioles.