Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion--evidence for retinoid signaling pathways in the mast cell lineage.
Investigation of mast cell responsiveness toward retinoic acid (RA) revealed selective promotion of ICAM-3 expression in the human mast cell line HMC-1. This process was dose- and time-dependent and detectable by flow cytometry, Western blot analysis, ELISA, and Northern blot analysis. ICAM-3 modulation was found to be cell-type dependent, detectable also for HL-60 cells and monocytes but not U-937 and only weakly for KU812 cells. Terminally differentiated skin mast cells also failed to up-modulate their ICAM-3, suggesting the requirement for some degree of immaturity for the process. RA-mediated effects on ICAM-1 expression, studied in parallel, were clearly distinct from those on ICAM-3. Investigation of retinoid receptor expression, known to mediate intracellular RA signaling, revealed presence of RAR alpha, RAR gamma, RXR beta, and RXR gamma transcripts in all cell lines studied, and HMC-1 cells were the only line lacking RXR alpha. RAR beta, not expressed at baseline, was induced by RA in a fashion obviously correlating with ICAM-3 up-regulation. Increased ICAM-3 expression was of functional significance, such that processes stimulated or co-stimulated via ICAM-3 (homotypic aggregation, IL-8 secretion) were clearly enhanced upon RA pretreatment, suggesting that RA may contribute via hitherto unrecognized pathways to immune function and host defense.
Department of Dermatology, Charité, Humboldt-Universität zu Berlin, Germany. magda.babina@charite.de
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D000077556:Alitretinoin; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000378:metabolism; D015474:Isotretinoin / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000096:biosynthesis / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D016209:Interleukin-8; D018168:Receptors, Retinoic Acid; D018799:Intercellular Adhesion Molecule-1; D000077556:Alitretinoin; D014212:Tretinoin; D015474:Isotretinoin