EXPRESSION OF VCAM-1 (CD106) BY A SUBSET OF TCR-GAMMA-DELTA-BEARING LYMPHOCYTE CLONES - INVOLVEMENT OF A METALLOPROTEASE IN THE SPECIFIC HYDROLYTIC RELEASE OF THE SOLUBLE ISOFORM

The cytokine-inducible vascular cell adhesion molecule 1/CD106 is wide ly distributed in endothelial, epithelial, macrophage, and dentritic c ells. We previously have reported a mAb termed sTA that recognizes the CD106 molecule on various TCR gamma delta T cell clones that do not p roliferate in response to an anti-CD3 stimulation. In the present repo rt, further biochemical analysis reveals two intracellular precursors (82 and 98 kDa) of the membrane-bound 110-kDa form of CD106. In additi on, we detect a 100-kDa soluble form in the culture supernatant of the specific cloned lymphocytes. Phorbol ester raises the amount of the s oluble CD106 in the supernatant while simultaneously inducing the disa ppearance of the membrane-bound form. We show that the membrane-anchor ed form of CD106 is converted to soluble form by a regulated proteolyt ic cleavage process involving a metalloprotease. EDTA and 1,10-phenant hroline, two potent inhibitors of metalloproteases, specifically inhib it the conversion of the membrane anchored to the soluble form of the CD106 molecule. In fact, these results implicate a Zn2+-activated meta lloprotease in the regulation of CD106 expression in a subset of T cel ls and, therefore, represent a novel pathway of T cell functions.