IgA-mediated effector function of HL-60 cells following treatment with calcitriol.
When cells of the HL-60 promyelocytic leukemia line are cultured with 1,25-dihydroxyvitamin D3 (calcitriol) they acquire a more highly differentiated, myelomonocytic phenotype. It was observed that the ability to ingest IgA-coated erythrocytes and to bind soluble dimeric IgA accompanied this maturation. Phagocytosis of IgA-coated erythrocytes was greater than 50% inhibited by 0.8 mg/ml free IgA, and not by IgG or IgM. Similarly, binding of dimeric IgA was not blocked by a 100-fold excess of IgG, IgM or IgE. Both IgA-mediated phagocytosis and IgA binding became apparent after two days of culture with calcitriol and increased with time in culture. The induction of functional IgA receptors was evident with 10(-11) M calcitriol and maximal levels of IgA binding and of numbers of cells capable of IgA mediated phagocytosis were induced by 10(-8)-10(-9) M calcitriol. 25-Hydroxyvitamin D3, which binds 100-1000-fold less avidly to the cytoplasmic D3 receptor than calcitriol, did not induce functional IgA receptors unless concns of 10(-7) M were used. Other compounds which induce differentiation of HL-60 cells, including retinoic acid and DMSO, produced similar results to calcitriol, whereas cells treated with gamma interferon expressed lower levels of IgA binding and did not ingest IgA-coated targets, suggesting that a critical density of IgA receptors must be reached to enable phagocytosis and/or that other cell activational events are required for IgA receptors to mediate killing. This model may provide useful insight into the function and regulation of IgA receptors on cells of the myeloid series.
Shen
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L
Maliszewski
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Rigby
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Fanger
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D015703:Antigens, CD; D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D011961:Receptors, Fc / Q000096:biosynthesis*
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011961:Receptors, Fc; D002117:Calcitriol; D002112:Calcifediol