Synthesis in vitro of 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 by interferon-gamma-stimulated normal human bone marrow and alveolar macrophages.
Cultured human macrophages from normal donors were examined for their capability to metabolize 25-hydroxyvitamin D3 (25-(OH)D3). Upon exposure to recombinant human interferon-gamma (IFN-gamma) both bone marrow-derived macrophages (BMM) and pulmonary alveolar macrophages (PAM) produced a polar 25-(OH)D3 metabolite which was purified from conditioned media and unequivocally identified as 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) by UV-absorbance spectrophotometry and mass spectrometry. The BMM and PAM also synthesized a second 25-(OH)D3 metabolite which was structurally identified as 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3). The time course of 25-(OH)D3 metabolism by macrophages suggested that the production of 24,25-(OH)2D3 was stimulated by high intracellular levels of 1,25-(OH)2D3 and not by IFN-gamma. The 1,25-(OH)2D3 obtained from BMM and PAM promoted macrophage-like differentiation of promyelocytic HL-60 leukemia cells and inhibited IFN-gamma production by normal human lymphocytes. Our data suggest that locally high levels of 1,25-(OH)2D3 in the microenvironment of IFN-gamma-stimulated BMM and PAM may modulate the function of hormone-responsive cells.
D015650:24,25-Dihydroxyvitamin D 3; D001854:Bone Marrow Cells; D002117:Calcitriol / Q000096:biosynthesis*; D002454:Cell Differentiation; D002460:Cell Line; D004100:Dihydroxycholecalciferols / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007938:Leukemia / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D013058:Mass Spectrometry; D011650:Pulmonary Alveoli / Q000166:cytology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet
D004100:Dihydroxycholecalciferols; D011994:Recombinant Proteins; D015650:24,25-Dihydroxyvitamin D 3; D007371:Interferon-gamma; D002117:Calcitriol