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Am J Physiol Heart Circ Physiol 272: H1725-H1729, 1997;
0363-6135/97 $5.00
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AJP - Heart and Circulatory Physiology, Vol 272, Issue 4 1725-H1729, Copyright © 1997 by American Physiological Society


ARTICLES

Cytokine-induced leukocyte rolling in mouse cremaster muscle arterioles in P-selectin dependent

H. Thorlacius, L. Lindbom and J. Raud
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Leukocyte rolling and adhesion are generally observed in venules but rarely observed in arterioles. With the use of intravital microscopy, we found that a 4-h treatment with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) dose dependently induced leukocyte rolling and adhesion in arterioles of the mouse cremaster muscle. The rolling response lasted more than 24 h and was completely inhibited by treatment with the sulfated polysaccharide fucoidin. Moreover, we found that costimulation with IL-1beta and TNF-alpha for 4 h synergistically increased arteriolar leukocyte rolling, i.e., threshold doses of IL-1beta and TNF-alpha together caused a more than 10-fold increase of rolling in arterioles compared with the sum of the individual responses. This rolling interaction was abolished by treatment with a monoclonal antibody directed against P-selectin (RB40.34), but it apparently was unaffected by a monoclonal antibody against L-selectin (MEL-14). Taken together, our functional data show that IL-1beta and TNF-alpha separately induce and synergistically increase P-selectin-dependent leukocyte rolling and firm adhesion in mouse cremaster arterioles.


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