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 mononuclear leukocytes. The objective of this study was to determine whether neutrophils can also express beta 1-integrin (specifically alpha 4 beta 1) and whether this can support neutrophil adhesion to endothelial cells and to extracellular matrix. We stimulated neutrophils with dihydrocytochalasin B (DHCB) and various chemotactic stimuli and observed 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 inhibitable by anti-CD18 antibody. beta 2-integrin-deficient cells, which did not respond to chemotactic stimuli alone, also adhered avidly in the presence of chemotactic stimuli and DHCB. The induced neutrophil adhesion 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 neutrophils induced by chemotactic stimuli alone also increased expression of beta 1 and alpha 4. Transmigration across deendothelialized membranes induced a similar beta 1 expression on neutrophils suggesting that events other than an endothelial signal elicited beta 1-integrin expression. Transmigration-induced beta 1-dependent expression translated into only modest adhesion to protein-coated plastic. These data suggest that both a pharmacological (DHCB) and a physiological (transmigration) stimulus can invoke expression of alpha 4 and beta 1 on human neutrophils to mediate adhesion.
Kubes
P
P
Immunology Research Group, University of Calgary, Alberta, Canada.
Niu
X F
XF
Smith
C W
CW
Kehrli
M E
ME
Reinhardt
P H
PH
Woodman
R C
RC
D015703:Antigens, CD / Q000502:physiology; D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D003571:Cytochalasin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology
D015703:Antigens, CD; D018821:CD18 Antigens; D003572:Cytochalasins; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D039441:Integrin alpha4; C024794:dihydrocytochalasin B; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine