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.
Kunkel
E J
EJ
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908, USA.
Jung
U
U
Ley
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D019556:COS Cells; D002448:Cell Adhesion; D019040:E-Selectin / Q000096:biosynthesis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis / Q000502:physiology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply*; D019007:P-Selectin / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D019007:P-Selectin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin