1,25-Dihydroxyvitamin D 3 Stimulates Phagocytosis but Suppresses HLA-DR and CD13 Antigen Expression in Human Mononuclear Phagocytes

Abstract

Abstract

This study investigated the regulatory activity of 1,25-dihydroxyvitamin D₃ (1,25-[OH]₂D₃) on phagocytic cells obtained from normal human peripheral blood. Flow cytometric analysis enabled identification of two discrete populations of cells, one predominantly monocytes (“monocyte” gate) and one containing primarily lymphoid and other cell types (“lymphoid” gate). The monocyte-associated antigens CD13 and CD33 were highly expressed by cells in this monocyte gate and used to monitor this population. Following 5 days of culture, cells in the monocyte 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)₂D₃ profoundly upregulated phagocytic activity while downregulating HLA-DR antigen expression on the cells in the monocyte gate. Moreover, 1,25-(OH)₂D₃ 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)₂D₃ and 24,25-(OH)₂D₃ metabolites indicated the regulatory effects are likely mediated by the 1,25-(OH)₂D₃ receptor (VDR).

Prostaglandin E₂ (PGE₂), a known modulator of monocyte/macrophage activity also markedly inhibited HLA-DR expression while enhancing the phagocytic activity of cells in the monocyte gate. In contrast to 1,25-(OH)₂D₃, PGE₂ clearly upregulated CD13 expression in cells with high phagocytic activity. Since indomethacin, an inhibitor of PGE₂ synthesis, failed to reverse the 1,25-(OH)₂D₃ induced inhibitory effect on HLA-DR expression, this effect is apparently not mediated through endogenous PGE₂ synthesis. Based on these findings we speculate that 1,25-(OH)₂D₃ may be capable of acting as both an upregulating agent during natural immunity via the enhancement of phagocytosis by monocyte/macrophage populations and as a “downregulator” during acquired immune responses via an inhibitory effect on MHC class II antigen expression by professional antigen-presenting cells. [P.S.E.B.M. 1996, Vol 211]