MODULATION OF VITAMIN-D INCREASED H2O2 PRODUCTION AND MAC-2 EXPRESSION IN THE BONE-MARROW-DERIVED MACROPHAGES BY ESTROGEN

The calcium-regulating hormone 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D -3) is recognized as an immunomodulator. Members of the macrophage-mon ocyte lineage are targets for 1,25(OH)(2)D-3 action. The hormone enhan ces the ability of bone marrow-derived macrophages (BMDMs) to produce H2O2, increases the expression of the macrophage specific surface anti gen MAC-2, increases the release of tumor necrosis factor-alpha (TNF-a lpha), and inhibits BMDM proliferation. In the present study we examin e the possibility that estrogen modulates 1,25(OH)(2)D-3 effects on BM DMs. The active form, 17 beta-estradiol, failed to affect any of the B MDM functions by itself. On the other hand, 17 beta-estradiol increase d the effects of 1,25(OH)(2)D-3 production by BMDMs and on MAC-2 expre ssion on these cells. The inactive estrogen analog 17 alpha-estradiol was unable to elicit these effects. Moreover, 17 beta-estradiol did no t affect the lipopolysaccharide (LPS)-induced increase in H2O2 product ion by BMDMs. Modulation of BMDM proliferation and TNF-alpha release f rom these cells by 1,25(OH)(2)D-3 were not affected by the estrogen. T he experiments were performed with BMDMs harvested from vitamin D-depl eted and repleted mice, and always under similar conditions, the vario us functions were more pronounced in the cells derived from the replet ed mice. Our data are consistent with the hypothesis that 17 beta-estr adiol modulates the interactions of 1,25(OH)(2)D-3 with BMDMs and cons equently is able to affect biological responses to 1,25(OH)(2)D-3 in t hese cells. We propose that this cell system is a convenient, nontrans formed model for studying cellular activities of 1,25(OH)(2)D-3.