Abstract
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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Aminoquinolines / pharmacology
-
Calcineurin
-
Calmodulin-Binding Proteins / antagonists & inhibitors*
-
Calmodulin-Binding Proteins / physiology
-
Carrier Proteins / metabolism
-
Chemotaxis, Leukocyte / drug effects*
-
Ethers, Cyclic / pharmacology
-
Glycoproteins*
-
Humans
-
Kinetics
-
Molecular Sequence Data
-
N-Formylmethionine Leucyl-Phenylalanine / pharmacology
-
Neutrophils / cytology
-
Neutrophils / drug effects
-
Neutrophils / physiology*
-
Okadaic Acid
-
Peptide Fragments / pharmacology
-
Peptides / pharmacology
-
Phosphoprotein Phosphatases / antagonists & inhibitors*
-
Phosphoprotein Phosphatases / physiology
-
Phosphorylation
-
Tacrolimus / pharmacology
-
Tacrolimus Binding Proteins
-
Vitronectin
Substances
-
Aminoquinolines
-
Calmodulin-Binding Proteins
-
Carrier Proteins
-
Ethers, Cyclic
-
Glycoproteins
-
Peptide Fragments
-
Peptides
-
Vitronectin
-
Cn 412
-
Okadaic Acid
-
N-Formylmethionine Leucyl-Phenylalanine
-
Calcineurin
-
Phosphoprotein Phosphatases
-
Tacrolimus Binding Proteins
-
Quin2
-
Tacrolimus