Inhibition of neutrophil chemokinesis on vitronectin by inhibitors of calcineurin.
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.
Hendey
B
B
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Klee
C B
CB
Maxfield
F R
FR
D000595:Amino Acid Sequence; D000634:Aminoquinolines / Q000494:pharmacology; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004988:Ethers, Cyclic / Q000494:pharmacology; D006023:Glycoproteins; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019319:Okadaic Acid; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000502:physiology; D010766:Phosphorylation; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins; D019096:Vitronectin
D000634:Aminoquinolines; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D004988:Ethers, Cyclic; D006023:Glycoproteins; D010446:Peptide Fragments; D010455:Peptides; D019096:Vitronectin; C077235:Cn 412; D019319:Okadaic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D022021:Tacrolimus Binding Proteins; C035739:Quin2; D016559:Tacrolimus