Soluble VCAM-1 binding to alpha 4 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 inf lammation and can alter lymphocyte functions. The authors report that the b inding of sVCAM-1 to alpha 4 integrin-bearing cells is a dynamically regula ted, active cellular process. Binding of recombinant sVCAM-1 to alpha 4 int egrins on peripheral blood mononuclear cells was cell-type specific. Circul ating CD16+ NK cells constitutively bound sVCAM-1 with high affinity, where as a subpopulation of T-lymphocytes, primarily CD45RO+ (memory), bound sVCA M-1 only after phorbol ester stimulation. sVCAM-1 binding to homogenous sta ble cell lines was also cell-type specific, and required active cellular pr ocesses because it was blocked by the inhibition of ATP synthesis and by Fa s-induced apoptosis, Indeed, the loss of high-affinity VCAM-1 binding was a n early event in apoptosis. Furthermore, an H-Ras/Raf-initiated signaling p athway also suppressed sVCAM-1 binding to alpha 4 beta 1 integrins. Collect ively, these results showed that the capacity of alpha 4 integrins to bind VCAM-1 is actively regulated and that this regulation may control alpha 4 i ntegrin-dependent cellular functions.