Impaired bone marrow-derived macrophage differentiation in vitamin D deficiency.
The calcium-regulating hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is also recognized as an immunomodulator. In vitro addition of the hormone to bone marrow-derived macrophages (BMDMs) results in a decreased proliferation and an increased differentiation. In the present work we compare the in vitro differentiation of BMDMs derived from vitamin D-depleted and -repleted mice (-D and +D BMDMs, respectively). -D BMDMs proliferate in vitro slower than +D BMDMs. Addition of the hormone to BMDM cultures inhibited the rate of their proliferation, which was more pronounced in low-density cultures. The ability of mononuclear phagocytes to produce reactive oxygen metabolites is an important element in the microbicidal functions of these cells. We found that -D BMDMs produce less H2O2 than +D BMDMs, which was corrected by the in vitro addition of 1,25(OH)2D3. Analyses of various macrophage-specific surface antigens revealed a reduction in their expression on -D BMDMs. In vitro addition of 1,25(OH)2D3 to BMDM cultures increased the expression of these antigens. The activity of the lysosomal enzyme acid phosphatase was similarly affected by vitamin D deficiency and by the in vitro addition of the hormone. Thus, vitamin D deficiency is associated with impaired maturation of BMDMs suggesting that the hormone is a natural modulator of macrophage maturation.
Abu-Amer
Y
Y
Hubert Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Bar-Shavit
Z
Z
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D014808:Vitamin D Deficiency / Q000276:immunology
D000954:Antigens, Surface; D002762:Cholecalciferol; D006861:Hydrogen Peroxide