Soluble VCAM-1 binding to alpha4 integrins is cell-type specific and activation dependent and is disrupted during apoptosis in T cells.
Soluble vascular cell adhesion molecule-1 (sVCAM-1) is generated during inflammation and can alter lymphocyte functions. The authors report that the binding of sVCAM-1 to alpha4 integrin-bearing cells is a dynamically regulated, active cellular process. Binding of recombinant sVCAM-1 to alpha4 integrins on peripheral blood mononuclear cells was cell-type specific. Circulating CD16+ NK cells constitutively bound sVCAM-1 with high affinity, whereas a subpopulation of T-lymphocytes, primarily CD45RO+ (memory), bound sVCAM-1 only after phorbol ester stimulation. sVCAM-1 binding to homogenous stable cell lines was also cell-type specific, and required active cellular processes because it was blocked by the inhibition of ATP synthesis and by Fas-induced apoptosis. Indeed, the loss of high-affinity VCAM-1 binding was an early event in apoptosis. Furthermore, an H-Ras/Raf-initiated signaling pathway also suppressed sVCAM-1 binding to alpha4beta1 integrins. Collectively, these results showed that the capacity of alpha4 integrins to bind VCAM-1 is actively regulated and that this regulation may control alpha4 integrin-dependent cellular functions. (Blood. 2000;95:602-609)
Rose
D M
DM
Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cardarelli
P M
PM
Cobb
R R
RR
Ginsberg
M H
MH
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology; D006801:Humans; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D019169:Jurkat Cells; D015471:Leukemia, Basophilic, Acute; D008213:Lymphocyte Activation; D051381:Rats; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D019014:fas Receptor / Q000502:physiology
D015703:Antigens, CD; D039041:Integrin alpha4beta1; D016023:Integrins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016201:Receptors, Lymphocyte Homing; D011993:Recombinant Fusion Proteins; D019010:Vascular Cell Adhesion Molecule-1; D019014:fas Receptor; D039441:Integrin alpha4