REGULATION OF SIALOADHESIN EXPRESSION ON RAT MACROPHAGES - INDUCTION BY GLUCOCORTICOIDS AND ENHANCEMENT BY IFN-BETA, IFN-GAMMA, IL-4, AND LIPOPOLYSACCHARIDE

Sialoadhesin is a macrophage-restricted member of the Ig superfamily t hat mediates adhesion with lymphoid and myeloid cells, It is expressed on a subpopulation of macrophages in lymphoid tissues and in chronic inflammation (e.g., during autoimmune diseases). We have studied the r egulation of sialoadhesin expression in vitro and show that glucocorti coids (CC) induce sialoadhesin expression on freshly isolated rat macr ophages and the rat macrophage cell line R2. The cytokines IFN-beta, I FN-gamma, IL-4, and LPS, although unable to induce sialoadhesin expres sion by themselves, were able to enhance CC-mediated induction of sial oadhesin. Sialoadhesin expression was functional as shown by cell adhe sion assays with human RBCs. Northern blotting experiments indicated t hat regulation predominantly occurred at the mRNA level, Comparison of the different combinations of GC and cytokines/LPS revealed differenc es in the level of CC-dependent enhancement of sialoadhesin expression , with IFN-beta and IL-4 being more potent than IFN-gamma and LPS. Mor eover, the effects of IFN-gamma and LPS could be reproduced by priming , whereas IFN-beta and IL-4 were required simultaneously with GC, The regulation of sialoadhesin expression was mediated by the CC receptor, and not by mineralocorticoid receptor, as shown by inhibition experim ents with specific antagonists, Finally, it is demonstrated that macro phages in the adrenal gland, the major site of endogenous GC productio n, express sialoadhesin. This study demonstrates that GC act as a prim ary inducer of sialoadhesin expression on rat macrophages, and that th e response can be enhanced by IFN-beta, T cell-derived cytokines, or L PS.