A HISTAMINE DERIVATIVE INCREASES INTRACELLULAR CALCIUM MOBILIZATION AND OXIDATIVE-METABOLISM IN HL-60 CELLS

Citation
R. Qiu et al., A HISTAMINE DERIVATIVE INCREASES INTRACELLULAR CALCIUM MOBILIZATION AND OXIDATIVE-METABOLISM IN HL-60 CELLS, Immunopharmacology, 26(3), 1993, pp. 213-224
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy",Immunology
Journal title
ISSN journal
0162-3109
Volume
26
Issue
3
Year of publication
1993
Pages
213 - 224
Database
ISI
SICI code
0162-3109(1993)26:3<213:AHDIIC>2.0.ZU;2-2
Abstract
Past work in our laboratory has shown that a derivative of histamine, histamine-trifluoromethyl-toluidide (HTMT), has surprising tissue spec ificity on lymphocytes and can produce remarkable immunosuppression. T his study focuses on the effects of HTMT on Ca2+ mobilization and oxid ative metabolism in undifferentiated and DMSO-differentiated HL-60 cel ls. HTMT caused two phases of increases in intracellular calcium conce ntrations ([Ca2+](i)) in HL-60 cells. The responses were dose dependen t, with similar EC(50) values (1.7 x 10(-5)M for undifferentiated and 1.5 x 10(-5)M for differentiated cells). The increase in [Ca2+]i in di fferentiated cells was much greater than in undifferentiated cells. Th e maximum responses were observed after the undifferentiated cells wer e incubated with DMSO for 7 days. The increase in [Ca2+](i) induced by HTMT in both types of cells was competitively antagonized by high con centrations of histamine but not by classic histamine receptor antagon ists (H-1, H-2, or H-3). The inhibitory effects of histamine on [Ca2+] (i) accumulation in differentiated cells were partially reversed by hi stamine H-2 receptor antagonist ranitidine, whereas in undifferentiate d cells, the effects of histamine on Ca2+ mobilization were not affect ed by ranitidine. Other cAMP elevating agents did not inhibit increase s in [Ca2+](i) in undifferentiated cells but did affect [Ca2+](i) in d ifferentiated cells. The enhanced response in [Ca2+](i) mobilization a fter differentiation of HL-60 cells appeared to be the result of an in crease in the expression/function of receptors for HTMT. One interesti ng feature of this regulation was the fact that cAMP per se did not re gulate HTMT induced Ca2+ mobilization in undifferentiated cells but in hibited the mobilization in differentiated cells. HTMT caused the gene ration of reactive oxygen species in both undifferentiated and differe ntiated HL-60 cells as measured by chemoluminescence and the levels of generation correlated with the mobilization of [Ca2+](i). In addition , the EC(50)s for the HTMT induced calcium mobilization and the genera tion of reactive oxygen species were similar, as was the case for hist amine induced inhibition (K-i) in both cell types. The data imply a se cond messenger role for Ca2+ in HTMT induced neutrophil activation.