PMID- 1645714 OWN - NLM STAT- MEDLINE DCOM- 19910710 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 266 IP - 17 DP - 1991 Jun 15 TI - Disassociation of the macrophage-maturational effects of vitamin D from respiratory burst priming. PG - 10888-92 AB - During the process of enhancing monocytic differentiation of the human leukemia line HL-60, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) also "primes" the cell for respiratory burst by increasing the uptake of Ca2+ across the plasma membrane (Hruska, K.A., Bar-Shavit, Z., Malone, J.D., and Teitelbaum, S.L. (1988) J. Biol. Chem. 263, 16039-16044). The present study asked if the maturational effect of vitamin D is dependent upon this "priming" phenomenon. To this end, we exposed HL-60 to either 1,25(OH)2D3 or its synthetic analogue (1 alpha, 3 beta, 5Z, 7E)-9-10-Secocholesta-5,7,10(19)-triene-1, 3, 25-triol (22-oxa). We found that 22-oxa induced HL-60 maturation as effectively as does the natural steroid. As expected, 48 h of 1,25(OH)2D3 exposure more than doubles (p less than 0.005) HL-60 basal cytosolic Ca2+ and increases inositol triphosphate-sensitive Ca2+ stores approximately 4-fold (p less than 0.01). 22-oxa in contrast alters neither Ca(2+)- nor inositol triphosphate-mobilizable deposits. Moreover, 1,25(OH)2D3 treatment prompts a transient Ca2+ "spike" in response to formyl-methionyl-leucyl-phenylalanine (fMLP) and a marked increase in superoxide (O-2) generation when exposed to the chemotactic peptide (p less than 0.01) or phorbol ester (p less than 0.02). Treatment with 22-oxa does not enable HL-60 to respond to fMLP with a Ca2+ spike or prime the cell for respiratory burst unless it is co-incubated with the Ca2+ ionophore, ionomycin. Similarly, phorbol ester impacts more profoundly on O-2 generation by 1,25(OH)2D3 than 22-oxa preincubated cells (p less than 0.02), unless the latter is added with ionomycin. Our findings indicate that the maturational effects of vitamin D sterols are independent of their capacity to prime cells for respiratory burst and that the Ca2+ ionophoretic effects of 1,25(OH)2D3 play a major role in such priming. FAU - Tanaka, H AU - Tanaka H AD - Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110. FAU - Hruska, K A AU - Hruska KA FAU - Seino, Y AU - Seino Y FAU - Malone, J D AU - Malone JD FAU - Nishii, Y AU - Nishii Y FAU - Teitelbaum, S L AU - Teitelbaum SL LA - eng GR - AR32087/AR/NIAMS NIH HHS/United States GR - DE05413/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Antineoplastic Agents) RN - 0 (Receptors, Calcitriol) RN - 0 (Receptors, Formyl Peptide) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Steroid) RN - 11062-77-4 (Superoxides) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - FXC9231JVH (Calcitriol) RN - N2UJM5NBF6 (maxacalcitol) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - SY7Q814VUP (Calcium) SB - IM MH - Antineoplastic Agents/pharmacology MH - Calcitriol/*analogs & derivatives/metabolism/*pharmacology MH - Calcium/*metabolism MH - Cell Differentiation/*drug effects MH - Cell Line MH - Cytoplasm/metabolism MH - Humans MH - Leukemia, Promyelocytic, Acute MH - Macrophages/*cytology/drug effects MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Receptors, Calcitriol MH - Receptors, Formyl Peptide MH - Receptors, Immunologic/drug effects/metabolism MH - Receptors, Steroid/drug effects/*metabolism MH - Superoxides/*metabolism MH - Tetradecanoylphorbol Acetate/pharmacology EDAT- 1991/06/15 00:00 MHDA- 1991/06/15 00:01 CRDT- 1991/06/15 00:00 PHST- 1991/06/15 00:00 [pubmed] PHST- 1991/06/15 00:01 [medline] PHST- 1991/06/15 00:00 [entrez] AID - S0021-9258(18)99102-7 [pii] PST - ppublish SO - J Biol Chem. 1991 Jun 15;266(17):10888-92.