Soluble VCAM-1 binding to a4 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 a4 integrinbearing cells is a dynamically regulated, active cellular process. Binding of recombinant sVCAM-1 to a4 integrins on peripheral blood mononuclear cells was celltype specific. Circulating CD161 NK cells constitutively bound sVCAM-1 with high affinity, whereas a subpopulation of T-lymphocytes, primarily CD45RO1 (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 a4b1 integrins. Collectively, these results showed that the capacity of a4 integrins to bind VCAM-1 is actively regulated and that this regulation may control a4 integrin-dependent cellular functions. (Blood. 2000;95:602609)