The adhesion receptor CD-31 can be primed to rapidly adjust the neutrophil cytoskeleton.
The adhesion receptor CD-31 is expressed on neutrophils and endothelial cells and participates in transendothelial migration of neutrophils. Although necessary, information on CD-31-induced signaling and its influence on the shape-forming actin network is scarce. Here, we found that antibody engagement of CD-31 on suspended neutrophils triggered a prompt intracellular Ca(2+) signal, providing the cells had been primed with a chemotactic factor. Inhibition of Src-tyrosine kinases blocked this Ca(2+) signal, but not a fMet-Leu-Phe-induced Ca(2+) signal. Despite the ability of fMet-Leu-Phe to activate Src-tyrosine kinases, it did not per se induce tyrosine phosphorylation of CD-31. However, fMet-Leu-Phe did enable such a phosphorylation following an antibody-induced engagement of CD-31. This clustering also triggered a Ca(2+)-dependent depolymerization of actin and, surprisingly enough, a simultaneous polymerization. The ability of CD-31 to signal dynamic alterations in the cytoskeleton, particularly the Ca(2+)-induced actin depolymerization, further explains how neutrophils can squeeze themselves out between adjacent endothelial cells.
Dimitrijevic
Ivan
I
Experimental Pathology, Department of Laboratory Medicine, Lund University, U-MAS, Malmö, SE-205 02, Sweden.
Axelsson
Lena
L
Andersson
Tommy
T
D000199:Actins / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002630:Chemotactic Factors / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D000199:Actins; D000906:Antibodies; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019061:src-Family Kinases; D002118:Calcium