1,25-dihydroxycholecalciferol stimulates ICAM-1 expression of human alveolar macrophages in healthy controls and patients with sarcoidosis.
Synthesis and release of 1,25-dihydroxycholecalciferol (1, 25-(OH)2D2) by alveolar macrophages (AM) have been shown to be increased in granulomatous lung disease. ICAM-1 plays a major part in leukocyte homing to sites of chronic inflammation, which is a crucial step during the inflammatory response. Whether 1,25-(OH)2D2 alters the ICAM-1 expression of AM in humans has not been studied. Bronchoalveolar lavage (BAL) was performed in 12 healthy volunteers, in 13 patients with sarcoidosis (active disease n = 8, inactive disease n = 5), and in 9 patients with chronic bronchitis. AM were incubated with different concentrations of 1,25-(OH)2D2 (10(-11) to 10(-6) M) with and without priming with interferon-gamma (IFN-gamma) and with and without preincubation with 10(-8) M dexamethasone. In addition, the metabolites of vitamin D, 24, 25-dihydroxycholecalciferol and 25-hydroxycholecalciferol, were used. The AM expression of ICAM-1 (cELISA) and the release of tumor necrosis factor-alpha (TNF-alpha) (bioassay) by AM were determined. In healthy volunteers the ICAM-1 expression on AM was significantly and dose-dependently increased by 1,25-(OH)2D2, but not by 24, 25-dihydroxycholecalciferol and 25-hydroxycholecalciferol. Priming with IFN-gamma resulted in an additive effect. Preincubation with dexamethasone inhibited ICAM-1 expression. Addition of 1,25-(OH)2D2 after inhibition by dexamethasone increased ICAM-1 expression significantly. TNF-alpha secretion of AM from healthy volunteers was significantly reduced by 1,25-(OH)2D2. In sarcoidosis patients ICAM-1 expression was significantly higher compared with healthy volunteers. Incubation with 1,25-(OH)2D2 resulted in a further significant increase of ICAM-1 expression. TNF-alpha secretion of AM was increased compared with healthy volunteers. 1,25-(OH)2D2 reduced TNF-alpha secretion; however, this difference was not significant. 1, 25-(OH)2D2 has an immunomodulating effect on human AM both in healthy volunteers and in sarcoidosis patients with enhanced expression of ICAM-1. It may serve as an autocrine mediator in inflammatory lung disease.
Braun
J
J
Department of Medicine II, Medical University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Dinkelacker
C
C
Bohnet
S
S
Kreft
B
B
Dalhoff
K
K
D000328:Adult; D001991:Bronchitis / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002117:Calcitriol / Q000494:pharmacology*; D016022:Case-Control Studies; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002117:Calcitriol