25-Hydroxyvitamin D3 metabolism by lipopolysaccharide-stimulated normal human macrophages

J Clin Endocrinol Metab. 1987 Jan;64(1):1-9. doi: 10.1210/jcem-64-1-1.

Abstract

Cultured normal human pulmonary alveolar macrophages and peripheral blood monocyte-derived macrophages were studied for their capacity to metabolize [3H]25-hydroxyvitamin D3 (25OHD3). Incubation of macrophages with bacterial lipopolysaccharide (LPS) resulted in the conversion of [3H]25OHD3 to a more polar vitamin D3 metabolite (up to 15 pmol/10(6) cells). Untreated macrophages did not synthesize this metabolite. Several findings suggested that the metabolite was the biologically active form of vitamin D3, namely 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. (1) The metabolite comigrated with chemically synthesized 1,25-(OH)2D3 on four different high performance liquid chromatographic systems. (2) The metabolite had the same affinity for the chick intestinal 1,25-(OH)2D3 receptor as authentic 1,25-(OH)2D3. (3) The biological activity of the macrophage metabolite in vivo (stimulation of intestinal calcium absorption and bone calcium mobilization in rachitic chicks) was identical to the activity of chemically synthesized 1,25-(OH)2D3. The LPS-stimulated synthesis of the 1,25-(OH)2D3-like compound by macrophages was dose dependent in a linear fashion; a half-maximal response was typically found with 100-200 ng LPS/10(6) cells. Polymyxin B abolished the effects of LPS on 25OHD3 metabolism in macrophages. Our data suggest that LPS-stimulated macrophages can modulate, on a local level, the function of 1,25-(OH)2D3-responsive cells by releasing the 1,25-(OH)2D3-like metabolite.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Binding, Competitive
  • Calcifediol / metabolism*
  • Calcium / metabolism
  • Cells, Cultured
  • Chickens
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Humans
  • Intestinal Absorption
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Monocytes / metabolism
  • Pulmonary Alveoli / metabolism

Substances

  • Lipopolysaccharides
  • Calcifediol
  • Calcium