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Science 9 October 1992:
Vol. 258. no. 5080, pp. 296 - 299
DOI: 10.1126/science.1384129
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Articles

Science, Vol 258, Issue 5080, 296-299
Copyright © 1992 by American Association for the Advancement of Science

articles

Inhibition of neutrophil chemokinesis on vitronectin by inhibitors of calcineurin

B Hendey, CB Klee, and FR Maxfield

Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

Migration of human polymorphonuclear neutrophils on vitronectin is dependent on repeated transient increases in the concentration of intracellular free calcium ([Ca2+]i). A specific peptide inhibitor of the Ca(2+)-calmodulin-dependent phosphatase calcineurin was introduced into the cytoplasm of neutrophils. The peptide inhibited neutrophil migration on vitronectin by interfering with the release of the cells from sites of attachment. A similar reduction in motility on vitronectin occurred when cells were treated with the immunosuppressant FK506, which also inhibits calcineurin when bound to its binding protein, FKBP. These results indicate that a rise in [Ca2+]i reduces integrin-mediated adhesion to vitronectin by a mechanism that requires calcineurin activity.


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