EFFECTS OF 1-ALPHA,25-DIHYDROXYVITAMIN D-3 AND CYTOKINES ON THE EXPRESSION OF MHC ANTIGENS, COMPLEMENT RECEPTORS AND OTHER ANTIGENS ON HUMAN BLOOD MONOCYTES AND U937 CELLS - ROLE IN CELL-DIFFERENTIATION, ACTIVATION AND PHAGOCYTOSIS

The effect of calcitriol/1 alpha,25-dihydroxyvitamin D-3, alone and in combination with cytokines, on the expression of various antigens (Ag ) on human peripheral blood monocytes and U937 cells was studied by fl ow cytometry. Both constitutive and interferon-gamma (IFN-gamma), inte rleukin-4 (IL-4), IL-6 and tumour necrosis factor-alpha (TNF-alpha)-in duced human leucocyte antigen (HLA)-DR, HLA-DP and HLA-DQ Ag expressio n on monocytes was significantly down-regulated by calcitriol, IL-10 a nd transforming growth factor-beta (TGF-beta). The effects of calcitri ol were concentration dependent and reached maximal inhibitory levels after 3-5 days. Modulation of HLA-DR by calcitriol and IFN-gamma at th e protein level correlated with the amount of mRNA specific for the HL A-DR alpha-chain, as judged by Northern blot analysis. The basal as we ll as IL-4, IL-6, IFN-gamma, TNF-alpha and TGF-beta-driven levels of H LA-ABC Ag were significantly diminished by calcitriol. On U937 cells c alcitriol markedly induced CD11a and CD11b expression and weakly up-re gulated CD11c whereas on monocytes, constitutive CD11a, CD11c and CD11 c expression was significantly down-regulated by calcitriol. The expre ssion of CD14 Ag was strongly induced on U937 cells but only modestly on monocytes. Both the basal level of CD71 and IL-4, IFN-gamma or TNF- cc-driven expression was diminished on calcitriol-treated U937 cells. In addition, calcitriol suppressed the expression of CD71 Ag on monocy tes. The ability of monocytes to phagocytize opsonized Escherichia col i was diminished by calcitriol. Our results demonstrate that calcitrio l, alone or in combination with cytokines, modulates expression of MHC , CD11b, CD11c, CD14 and CD71 Ag on both monocytes and U937 cells, and impairs the phagocytic property of monocytes.