The effect of vitamin D analogs and of vitamin D-binding protein on lymphocyte proliferation.
In the absence of vitamin D-binding protein (DBP), 1,25-(OH)2D3 at 10(-12) M significantly inhibited the [3H]thymidine incorporation in human lymphocytes during mixed lymphocyte cultures (MLC) or after phyto-hemaglutinin (PHA) stimulation. In the presence of a physiological concentration of DBP (5 x 10(-6) M), the concentration of 1,25-(OH)2D3 required for inhibition was 10(-10) M (for PHA-cultures) and 10(-9) M (for MLC). Several vitamin D analogs were compared for their inhibitory action on PHA stimulation. In the absence of DBP, the concentration necessary for 50% inhibition of [3H]thymidine incorporation ranged from 10(-12) M [1,25-(OH)2D3 and 24,24-F2-1,25-(OH)2D3], over 10(-10) M [1,24R, 25-(OH)3D3; 1,25S, 26-(OH)3D3 and 26,27-F6-1,25-(OH)2D3] and 10(-8) M [25 OHD3 and 24,25-(OH)2D3] to 10(-6) M [calcitriol-lactone]. This rank order correlates with the binding affinity of the various analogs to the cytoplasmic 1,25-(OH)2D3-receptor. DBP counteracted the inhibitory effect of all analogs and the degree of counteraction was directly proportional to the binding affinity between DBP and the vitamin D analog. DBP thus decreased the in vitro inhibitory action of 1,25-(OH)2D3 and its analogs on lymphocyte proliferation. Of all analogs tested, only 1,25-(OH)2D3 had a significant effect at a physiological concentration.
Vanham
G
G
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Onderwijs en Navorsing, Leuven, Belgium.
Van Baelen
H
H
Tan
B K
BK
Bouillon
R
R
D002117:Calcitriol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects; D013329:Structure-Activity Relationship; D014809:Vitamin D-Binding Protein / Q000378:metabolism*
D014809:Vitamin D-Binding Protein; D002117:Calcitriol