Effects of 1 alpha,25-dihydroxyvitamin D3 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 D3, alone and in combination with cytokines, on the expression of various antigens (Ag) on human peripheral blood monocytes and U937 cells was studied by flow cytometry. Both constitutive and interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6 and tumour necrosis factor-alpha (TNF-alpha)-induced human leucocyte antigen (HLA)-DR, HLA-DP and HLA-DQ Ag expression on monocytes was significantly down-regulated by calcitriol, IL-10 and transforming growth factor-beta (TGF-beta). The effects of calcitriol were concentration dependent and reached maximal inhibitory levels after 3-5 days. Modulation of HLA-DR by calcitriol and IFN-gamma at the protein level correlated with the amount of mRNA specific for the HLA-DR alpha-chain, as judged by Northern blot analysis. The basal as well as IL-4, IL-6, IFN-gamma, TNF-alpha and TGF-beta-driven levels of HLA-ABC Ag were significantly diminished by calcitriol. On U937 cells calcitriol markedly induced CD11a and CD11b expression and weakly up-regulated CD11c whereas on monocytes, constitutive CD11a, CD11b and CD11c expression was significantly down-regulated by calcitriol. The expression 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-alpha-driven expression was diminished on calcitriol-treated U937 cells. In addition, calcitriol suppressed the expression of CD71 Ag on monocytes. The ability of monocytes to phagocytize opsonized Escherichia coli was diminished by calcitriol. Our results demonstrate that calcitriol, 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.
Spittler
A
A
Institute of General and Experimental Pathology, University of Vienna, Austria.
Willheim
M
M
Leutmezer
F
F
Ohler
R
R
Krugluger
W
W
Reissner
C
C
Lucas
T
T
Brodowicz
T
T
Roth
E
E
Boltz-Nitulescu
G
G
D015703:Antigens, CD / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D011951:Receptors, Complement / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D016207:Cytokines; D006680:HLA Antigens; D011951:Receptors, Complement; D009580:Nitroblue Tetrazolium; D002117:Calcitriol