1,25-dihydroxyvitamin D3 stimulates phagocytosis but suppresses HLA-DR and CD13 antigen expression in human mononuclear phagocytes.
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 carboxylmicrospheres 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 phagocyte 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.
Tokuda
N
N
Department of Urology, Kyushu Unversity, Fukuoka, Japan.
Levy
R B
RB
D018826:CD13 Antigens / Q000032:analysis*; D002117:Calcitriol / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*
D006684:HLA-DR Antigens; D018826:CD13 Antigens; D002117:Calcitriol; D015232:Dinoprostone