Tnf-[alpha] induces selectin-mediated leukocyte rolling in mouse
cremaster muscle arterioles.
Kunkel, Eric J., Unsu Jung, and Klaus Ley.
Department of Biomedical Engineering, University of Virginia School
of Medicine, Charlottesville, VA 22908
APStracts 3:0437H, 1996.
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 2-3 hour TNF
-[alpha] stimulation of the mouse cremaster muscle induces rolling in
arterioles (diameters, 30-70 [mu]m; 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 [mu]m (wall shear rates, 1,500-3,250 s-1).
The arteriolar rolling flux fraction in wild-type mice averaged 5%
and was blocked by the P-selectin mAb RB40.34. The rolling flux
fraction in L- and E-selectin deficient mice was similar to wild-type
mice and 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 50 [mu]m/s, but increased to 110 [mu]m/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 which requires E-selectin
for rolling at normal velocities.
Received 7 August 1996; accepted in final form 24 September 1996.
APS Manuscript Number H718-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996