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BACKGROUND: Although the adhesive mechanisms underlying the capture and immobilization of circulating neutrophils in inflamed blood vessels have been well described, factors controlling the subsequent migration of neutrophils over and through the blood vessel endothelium are poorly understood. Directional rearrangement of the actin cytoskeleton within the neutrophil, along with modulation of integrin-mediated adhesion, are necessary for neutrophil migration. Signals from chemotactic agents and from the adhesive substrate may regulate these processes, but little is known about their relative importance or their mode of integration. RESULTS: We examined the kinetics of neutrophil migration after formyl tripeptide or platelet-activating factor was perfused over neutrophils that were already rolling on the adhesion molecule P-selectin, which was presented either on the surface of immobilized platelets or in purified form coated on glass capillaries. Upon activation, neutrophils stopped rolling, spread and began to migrate; each of these processes was dependent on beta2 integrin (CD11b/CD18). The rate of migration increased over a period of about 8 minutes and was modulated directly by both the P-selectin and the CD31 surface receptors. Antibody blockade of either CD31 or P-selectin on platelets resulted in a reduction in the velocity of migration, and simultaneous blockade of both receptors reduced velocity further. Purified CD31 and P-selectin (but not a control adhesion molecule, ICAM-1) increased migration velocity in a concentration-dependent and additive manner that reconstituted the migratory behaviour observed on platelets. CONCLUSIONS: These studies show that binding of ligands to CD31 and/or P-selectin modifies the rate of integrin-supported neutrophil migration. This novel example of 'cross-talk' between surface receptors suggests that cell adhesion molecules might generally transduce accessory signals between adjacent cells to modify their migratory responses to chemotactic signals.


Journal article


Curr biol

Publication Date





316 - 325


Animals, Antibodies, Antigens, CD, Blood Platelets, CD18 Antigens, CHO Cells, Cell Adhesion, Cell Adhesion Molecules, Cell Communication, Cells, Immobilized, Chemotaxis, Leukocyte, Cricetinae, Humans, In Vitro Techniques, Intercellular Adhesion Molecule-1, Kinetics, Macrophage-1 Antigen, Models, Biological, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, P-Selectin, Platelet Endothelial Cell Adhesion Molecule-1, Recombinant Proteins, Transfection