1,25-DIHYDROXYVITAMIN D-3 STIMULATES PHAGOCYTOSIS BUT SUPPRESSES HLA-DR AND CD13 ANTIGEN EXPRESSION IN HUMAN MONONUCLEAR PHAGOCYTES

This study investigated the regulatory activity of 1,25-dihydroxyvitam in D-3 (1,25-[OH]D-2(3)) on phagocytic cells obtained from normal huma n peripheral blood, Flow cytometric analysis enabled identification of two discrete populations of cells, one predominantly monocytes (''mon ocyte'' gate) and one containing primarily lymphoid and other cell typ es (''lymphoid'' gate). The monocyte-associated antigens CD13 and CD33 were highly expressed by cells in this monocyte gate and used to moni tor this population. Following 5 days of culture, cells in the monocyt e gate manifested high phagocytic activity as determined by ingestion of fluorescent carboxyl microspheres and exhibited high expression of class II HLA-DR products. 1,25-(OH)(2)D-3 profoundly upregulated phago cytic activity while downregulating HLA-DR antigen expression on the c ells in the monocyte gate. Moreover, 1,25-(OH)(2)D-3 also reduced cell surface CD13 expression on the cells with low but not high phagocytic activity In this gate, Proportional activities by the 1,24-(OH)(2)D-3 and 24,25-(OH)(2)D-3 metabolites indicated the regulatory effects are likely mediated by the 1,25-(OH)(2)D-3 receptor (VDR). Prostaglandin E(2) (PGE(2)), a known modulator of monocyte/macrophage activity also markedly inhibited HLA-DR expression while enhancing the phagocytic ac tivity of cells in the monocyte gate. In contrast to 1,25-(OH)(2)D-3, PGE(2) clearly upregulated CD13 expression in cells with high phagocyt ic activity. Since indomethacin, an inhibitor of PGE(2) synthesis, fai led to reverse the 1,25-(OH)(2)D-3 induced inhibitory effect on HLA-DR expression, this effect is apparently not mediated through endogenous PGE(2) synthesis. Based on these findings we speculate that 1,25-(OH) (2)D-3 may be capable of acting as both an upregulating agent during n atural immunity via the enhancement of phagocytosis by monocyte/macrop hage populations and as a ''downregulator'' during acquired immune res ponses via an inhibitory effect on MHC class II antigen expression by professional antigen-presenting cells.