Leukotriene C4Uses a Probenecid-Sensitive Export Carrier that does not Recognize Leukotriene B4

The export of leukotriene (LT) C4from human eosinophils, a carrier-mediated process that is temperature-dependent and saturable, was characterized further in eosinophils and in two human leukemia cell lines that do not present an intact 5-lipoxygenase pathway. In eosinophils, KG-1 cells, and dimethy...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1992-12, Vol.89 (23), p.11598-11602
Main Authors: Lam, Bing K., Xu, Kongyi, Atkins, Michael B., Austen, K. Frank
Format: Article
Language:English
Subjects:
Anions
Cell lines
Cultured cells
Energy value
Eosinophils
Hematopoietic stem cells
Ice
Leukotrienes
Mast cells
Organic acids
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Summary:The export of leukotriene (LT) C4from human eosinophils, a carrier-mediated process that is temperature-dependent and saturable, was characterized further in eosinophils and in two human leukemia cell lines that do not present an intact 5-lipoxygenase pathway. In eosinophils, KG-1 cells, and dimethyl sulfoxide (DMSO)-differentiated HL-60 cells, the respective Q10values for temperature-dependent LTC4export were 3.7, 3.3, and 3.4 and for energy of activation were 28.2 kcal/mol, 23.0 kcal/mol, and 27.8 kcal/mol (1 kcal = 4.18 kJ). When human eosinophils, KG-1 cells, and DMSO-differentiated HL-60 cells were preloaded with defined amounts of intracellular LTC4by incubation with LAT4and with incremental amounts of a gluthathione conjugate, S-dinitrophenyl glutathione (GS-DNP) by sequential incubation with 1-chloro-2, 4-dinitrobenzene, GS-DNP inhibited the export of LTC4in a dose-dependent manner. By plotting the ratio of total GS-DNP (cell retained plus released) to the sum of total GS-DNP plus total LTC4against the percentage inhibition of LTC4release, IC40values of 0.839, 0.803, and 0.841 were obtained for eosinophils, KG-1 cels, and DMSO-differentiated HL-60 cells, respectively. Wen cells preloaded with LTC4were resuspended in incremental concentrations of the organic acid transport inhibitor, probenecid, there was a dose-dependent decrease in LTC4release; GS-DNP and probenecid inhibited LTC4release in a cumulative fashion, whereas neither inhibited the release of LTB4from preloaded nondifferentiated HL-60 cells. Therefore, LTC4export from cells of bone marrow origin occurs through a probenecid-sensitive membrane carrier shared by other glutathione conjugates and distinct from the LTB4carrier export system.
ISSN:0027-8424