Soluble and cell-associated forms of the adhesion molecule LFA-3 (CD58) are differentially regulated by inflammatory cytokines

The adhesion molecule lymphocyte function-associated antigen 3 (LFA-3) (CD5 8) is an important regulator of immune cell function which occurs as both s urface-associated and 'soluble' forms. This study has investigated the inte r-relationship and the effects of cytokines on the expression of LFA-3 isof orms. The surface antigen was found to be relatively unaffected by cytokine s, but the release of soluble LFA-3 (sLFA-3) was highly responsive to inter leukin 1 beta (IL-I beta), interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha). This modulation was cell-specific, particularly with regard to IFN-gamma, which upregulated sLFA-3 release by A43 1 cells b ut down-regulated the release of the soluble form from HEp2 and HepG2 cells . We further demonstrated that LFA-3 is also present in a cytoplasmic 'pool ' in each of the cells and, moreover, that cleavage of LFA- 3 from the cell surface by phospholipase C resulted in an increase in the levels of the in tracellular LFA-3 and replacement of the membrane-associated antigen. These observations suggest that the expression of the surface, soluble and intra cellular forms of LFA-3 may be linked by regulatory mechanisms which are li kely to exert an important influence on inflammatory interactions.