STIMULATION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) ANTIGEN EXPRESSION AND SHEDDING BY INTERFERON-GAMMA AND PHORBOL ESTER IN HUMAN RENAL-CARCINOMA CELL-CULTURES - RELATION TO PERIPHERAL-BLOOD MONONUCLEARCELL-ADHESION

In the present study we investigated the effect of interferon-gamma (I FN-gamma) and phorbol-12-myristate 13 acetate (PMA) on intercellular a dhesion molecule-1 (ICAM-1) antigen expression and shedding in human r enal carcinoma cell cultures. We also examined the functional conseque nces of ICAM-1 antigen expression and soluble ICAM-1 molecules on the adhesion of peripheral blood mononuclear cells (PBMC). Incubation of t he human renal carcinoma cell line CaKi-1 with IFN-gamma or PMA enhanc ed ICAM-1 antigen expression. The calcium ionophore, 4-bromo-calcium i onophore A23187 (Bromo-A23187) significantly enhanced the IFN-gamma an d PMA effect. Soluble ICAM-1 (sICAM-1) was detected in the supernatant s of stimulated but not unstimulated cultures, and correlated signific antly with cellular expression. Using Cr-51-labelled peripheral blood mononuclear cells in a cell adhesion assay, we demonstrated increased adhesion in IFN-gamma-treated CaKi-1 cultures, which was augmented by Bromo-A23187. This adhesion was blocked by preincubation of CaKi-1 cel ls with monoclonal antibody against ICAM-1 or by preincubation of PBMC with either monoclonal antibody against leucocyte function associated antigen-1 alpha (LFA-1 alpha), a major receptor for ICAM-1, supernata nts from treated cultures or purified sICAM-1 molecules. Thus, sheddin g of ICAM-1 may play a role during the escape from immunosurveillance by renal carcinoma cells.