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 widely distributed in endothelial, epithelial, macrophage, and dentritic cells. We previously have reported a mAb termed sTA that recognizes the CD106 molecule on various TCR gamma delta T cell clones that do not proliferate in response to an anti-CD3 stimulation. In the present report, further biochemical analysis reveals two intracellular precursors (82 and 98 kDa) of the membrane-bound 110-kDa form of CD106. In addition, we detect a 100-kDa soluble form in the culture supernatant of the specific cloned lymphocytes. Phorbol ester raises the amount of the soluble CD106 in the supernatant while simultaneously inducing the disappearance of the membrane-bound form. We show that the membrane-anchored form of CD106 is converted to soluble form by a regulated proteolytic cleavage process involving a metalloprotease. EDTA and 1,10-phenanthroline, two potent inhibitors of metalloproteases, specifically inhibit the conversion of the membrane anchored to the soluble form of the CD106 molecule. In fact, these results implicate a Zn(2+)-activated metalloprotease in the regulation of CD106 expression in a subset of T cells and, therefore, represent a novel pathway of T cell functions.
Leca
G
G
Association Claude Bernard, Saint Louis Hospital, Paris, France.
Mansur
S E
SE
Bensussan
A
A
D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000737:chemistry; D002454:Cell Differentiation; D002999:Clone Cells; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008666:Metalloendopeptidases / Q000378:metabolism*; D011233:Precipitin Tests; D011480:Protease Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D011480:Protease Inhibitors; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019010:Vascular Cell Adhesion Molecule-1; D011493:Protein Kinase C; D008666:Metalloendopeptidases; D013755:Tetradecanoylphorbol Acetate