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PMID: 3838552 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis.

The Journal of experimental medicine ·Vol. 161 ·No. 4 ·1985-04-01 ·Pages 755-65

Adams JS, Gacad MA

Abstract

We investigated the 1 alpha-hydroxylation of vitamin D3 sterols by cultured pulmonary alveolar macrophages (PAM) from patients with sarcoidosis with or without clinically abnormal calcium homeostasis. Like the naturally occurring renal 1 alpha-hydroxylase, the PAM 1 alpha-hydroxylation reaction exhibited a high affinity for 25-hydroxyvitamin D3 (25-OH-D3) and a preference for substrates containing a 25-hydroxyl group in the side chain of the sterol. Unlike the renal enzyme, the PAM 1 alpha-hydroxylating mechanism was not accompanied by 24-hydroxylating activity, even after preincubation with 75 nM 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3] or exposure to high concentrations of substrate (500 nM 25-OH-D3). The PAM 25-OH-D3-1 alpha-hydroxylation reaction was stimulated by gamma interferon and inhibited by exposure to the glucocorticoid dexamethasone. The characteristics of the PAM hydroxylation process in vitro appear to reflect the efficiency of the extrarenal production of 1,25-(OH)2-D3 and the therapeutic efficacy of glucocorticoids in patients with sarcoidosis and disordered calcium metabolism.

MeSH Terms
25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism Adult Calcitriol/biosynthesis Cells, Cultured Female Humans Hydroxylation Hypercalcemia/metabolism Kinetics Lung Diseases/metabolism Macrophages/metabolism Male Middle Aged Pulmonary Alveoli/cytology Sarcoidosis/metabolism Steroid Hydroxylases/metabolism Substrate Specificity
Chemicals
Steroid Hydroxylases 25-Hydroxyvitamin D3 1-alpha-Hydroxylase Calcitriol
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Adams J S
Gacad M A
References (22)
22 references, click to expand
  1. 1,24,25-Trihydroxyvitamin D3. A metabolite of vitamin D3 effective on intestine.
    J Biol Chem. 1973 Oct 10;248(19):6691-6 PMID: 4355503
  2. The human alveolar macrophage.
    Methods Cell Biol. 1980;21A:95-105 PMID: 6997688
  3. Silica Sep-Pak preparative chromatography for vitamin D and its metabolites.
    J Chromatogr. 1981 Nov 13;226(1):198-201 PMID: 6274889
  4. Regulation of 25 hydroxyvitamin D3 1-hydroxylase in serum-free monolayer culture of mouse kidney.
    Endocrinology. 1982 Mar;110(3):1073-5 PMID: 7035146
  5. Catalytic activity of partially purified renal 25-hydroxyvitamin D hydroxylases from vitamin D-deficient and vitamin D-replete rats.
    J Biol Chem. 1982 Nov 10;257(21):12995-3000 PMID: 6890063
  6. Lymphokines enhance the capacity of human monocytes to secret reactive oxygen intermediates.
    J Clin Invest. 1982 Nov;70(5):1042-8 PMID: 7130393
  7. 25-hydroxyvitamin D hydroxylation. Evidence for a dioxygenase activity of solubilized renal mitochondrial cytochrome P-450.
    J Biol Chem. 1983 Oct 10;258(19):11590-3 PMID: 6684659
  8. Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis.
    J Clin Invest. 1983 Nov;72(5):1856-60 PMID: 6688814
  9. Interstitial lung diseases of unknown cause. Disorders characterized by chronic inflammation of the lower respiratory tract.
    N Engl J Med. 1984 Jan 26;310(4):235-44 PMID: 6361563
  10. Abnormal regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase activity by calcium and calcitonin in renal cortex from hypophosphatemic (Hyp) mice.
    Endocrinology. 1984 Apr;114(4):1203-7 PMID: 6705736
  11. 1,25-dihydroxyvitamin D3: a novel immunoregulatory hormone.
    Science. 1984 Jun 29;224(4656):1438-40 PMID: 6427926
  12. Effect of cortisone on calcium metabolism in sarcoidosis with hypercalcaemia; possibly antagonistic actions of cortisone and vitamin D.
    Lancet. 1954 Oct 9;267(6841):720-4 PMID: 13202480
  13. Stimulation of 24,25-dihydroxyvitamin D3 production by 1,25-dihydroxyvitamin D3.
    Science. 1974 Mar;183(130):1198-1200 PMID: 4812350
  14. Mitochondrial cytochrome p450. A component of chick kidney 25-hydrocholecalciferol-1alpha-hydroxylase.
    J Biol Chem. 1974 May 25;249(10):3026-33 PMID: 4151488
  15. The 24-hydroxylation of 1,25-dihydroxyvitamin D3.
    J Biol Chem. 1977 Feb 25;252(4):1421-4 PMID: 838723
  16. Effects of 1 alpha,25-, 24R,25-, and 1 alpha,24R,25-hydroxylated metabolites of vitamin D3 on calcium and phosphate absorption by duodenum from intact and nephrectomized rats.
    Arch Biochem Biophys. 1977 Jul;182(1):251-7 PMID: 883833
  17. Regulation of the hydroxylation of 25-hydroxyvitamin D3 in vivo and in primary cultures of chick kidney cells.
    J Biol Chem. 1979 Apr 25;254(8):2722-9 PMID: 429315
  18. 1, 25-dihydroxycholecalciferol in the pathogenesis of the hypercalcaemia of sarcoidosis.
    Lancet. 1979 Mar 24;1(8117):627-30 PMID: 85869
  19. Evidence that increased circulating 1 alpha, 25-dihydroxyvitamin D is the probable cause for abnormal calcium metabolism in sarcoidosis.
    J Clin Invest. 1979 Jul;64(1):218-25 PMID: 312811
  20. In vitro metabolism of 25-hydroxyvitamin D3 by isolated rat kidney cells.
    Proc Natl Acad Sci U S A. 1980 Mar;77(3):1537-40 PMID: 6929507
  21. Regulation of the metabolism of vitamin D.
    Physiol Rev. 1980 Apr;60(2):551-613 PMID: 6992167
  22. The synthesis of dihydroxylated vitamin D metabolites by human renal mitochondria.
    J Clin Endocrinol Metab. 1981 Aug;53(2):450-2 PMID: 6972950
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.161.4.755
Published
1985-04-01
Pages
755-65
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2189055
Subset
IM
Grants
NCRR NIH HHS · RR0043 · United States
External Links
PubMed source DOI: 10.1084/jem.161.4.755 PMC Full Text View journal details
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