TNF-alpha induces selectin-mediated leukocyte rolling in mouse cremaster muscle arterioles.

Leukocyte rolling is commonly restricted to venules and mediated by selectins expressed both on leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). We show here that 2- to 3-h tumor necrosis factor-alpha (TNF-alpha) stimulation of the mouse cremaster muscle induces rolling in arterioles (diameters 30-70 microm; wall shear rates 225-1,770 s(-1)). Weak P-selectin expression was detected on arteriolar endothelium of TNF-alpha-stimulated cremaster muscles. No rolling was observed in arterioles smaller than 30 microm (wall shear rates 1,500-3,250 s(-1)). The arteriolar rolling flux fraction in wild-type mice averaged approximately 5% and rolling was blocked by the P-selectin monoclonal antibody (MAb) RB40.34. Rolling in L- and E-selectin-deficient mice was similar to that in wild-type mice and was also blocked by the MAb RB40.34. Rolling was completely absent in arterioles of P-selectin-deficient mice. The average rolling velocity in arterioles of wild-type and L-selectin-deficient mice was approximately 50 microm/s but increased to approximately 110 microm/s in E-selectin-deficient mice and after injection of the blocking E-selectin MAb 9A9 in wild-type mice. We conclude that TNF-alpha treatment induces P-selectin-dependent rolling in arterioles that requires E-selectin for rolling at normal velocities.