Human leukemic (HMC-1) mast cells are responsive to 1alpha, 25-dihydroxyvitamin D(3): selective promotion of ICAM-3 expression and constitutive presence of vitamin D(3) receptor.
Expression levels of adhesion molecules on HMC-1 mast cells were examined prior to and following administration of 1alpha, 25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. While most receptors (including ICAM-1) remained unchanged by the treatment, solely ICAM-3 expression was promoted in a dose- and time-dependent fashion, peaking at 50 nM of 1,25(OH)(2)D(3) and 72 h, illustrating that like other myeloid cells, human mast cells are 1,25(OH)(2)D(3) responsive, yet in a highly selective manner. Flow cytometric results were confirmed by ELISA, by semiquantitative RT-PCR, and functionally by showing enhanced anti-ICAM-3 mediated homotypic aggregation of 1,25(OH)(2)D(3) pretreated cells. Since cellular responsiveness is conferred by the vitamin D(3) receptor (VDR), we examined human mast cells for its expression. VDR was constitutively present in both HMC-1 and skin mast cells by RT-PCR technique and in nuclear extracts of HMC-1 cells by Western blot analysis. Our data thus suggest that human mast cells are direct targets of 1, 25(OH)(2)D(3) action.
Babina
M
M
Department of Dermatology, Humboldt-Universität zu Berlin, Berlin, D-13344, Germany.
Krautheim
M
M
Grützkau
A
A
Henz
B M
BM
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D017931:DNA Primers; C483616:ICAM3 protein, human; D018167:Receptors, Calcitriol; D002117:Calcitriol