Metabolism of 25-OH-vitamin D3 by peritoneal macrophages from CAPD patients

The active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), is produced mainly by the kidney, but there is evidence for extrarenal production in certain circumstances. We studied whether peritoneal macrophages (PM) from CAPD patients were capable of metabolizing 25-OH-D3 to 1,25(OH)2D3. We found that PM were able to metabolize 25-OH-D3 in vitro; the main product following 16 hours of incubation was 19-nor, 10-oxo, 25-OH-D3 with smaller amounts of 1,25(OH)2D3. However, after shorter incubations of three and five hours a larger portion of 1,25(OH)2D3 was produced. The metabolism of 25-OH-D3 was greatly enhanced in PM harvested during episodes of peritonitis. This property was specific for PM of CAPD patients, and was not found in PM from normal subjects. However, incubation of control PM with peritoneal effluent from CAPD patients resulted in induction of the ability of these cells to metabolize 25-OH-D3. This induction was enhanced by preincubation with peritoneal effluent from CAPD patients suffering from peritonitis. Prostaglandin E2 was found to be involved in this synthesis: addition of PGE2 to normal PM induced metabolism of 25-OH-D3, and incubation of PM from CAPD patients with indomethacin decreased the metabolism of 25-OH-D3. The vitamin D metabolites produced by PM from CAPD patients could have a role in immunological resistance to peritoneal infections.