A NOVEL BETA(1)-DEPENDENT ADHESION PATHWAY ON NEUTROPHILS - A MECHANISM INVOKED BY DIHYDROCYTOCHALASIN-B OR ENDOTHELIAL TRANSMIGRATION

It is generally accepted that the beta(2)-integrin is restricted to mo nonuclear leukocytes. The objective of this study was to determine whe ther neutrophils can also express beta(1)-integrin (specifically alpha (4) beta(1)) and whether this can support neutrophil adhesion to endot helial cells and to extracellular matrix. We stimulated neutrophils wi th dihydrocytochalasin B (DHCB) and various chemotactic stimuli and ob served that chemotactic stimuli induced neutrophil adhesion via beta(2 )-integrin (CD18), whereas DHCB and either fMLP, PAF, or IL-8 induced adhesion to endothelium or protein-coated plastic that was not inhibit able by anti-CD18 antibody. beta(2)-integrin-deficient cells, which di d not respond to chemotactic stimuli alone, also adhered avidly in the presence of chemotactic stimuli and DHCB. The induced neutrophil adhe sion was inhibited by antibody to beta(1)- or alpha(4)-integrin chains , but only if an anti-beta(2)-integrin antibody was also present. Flow cytometry revealed increased expression of both beta(1) and alpha(4) in the presence of fMLP plus DHCB. Transendothelial migration of neutr ophils induced by chemotactic stimuli alone also increased expression of beta(1) and alpha(4). Transmigration across deendothelialized membr anes induced a similar beta(1) expression on neutrophils suggesting th at events other than an endothelial signal elicited beta(1)-integrin e xpression. Transmigration-induced beta(1)-dependent expression transla ted into only modest adhesion to protein-coated plastic. These data su ggest that both a pharmacological (DHCB) and a physiological (transmig ration) stimulus can invoke expression of alpha(4) and beta(1) on huma n neutrophils to mediate adhesion.