Erythrocytes increase leukotriene C4 release from human eosinophils: characterization and examination of possible mechanisms.
There has been considerable interest in the role of eosinophils in the pathogenesis of asthma and allergic diseases. While examining the conditions necessary for the release of leukotriene C4 (LTC4) from human eosinophils activated by immunoglobulin G-Sepharose (IgG-Seph), we observed that red blood cells (RBCs) potentiated eosinophil LTC4 release. The time course of IgG-Seph-stimulated LTC4 release was prolonged in the presence of RBCs. After 45 min of incubation, eosinophils without RBCs released 0.95 +/- 0.11 ng/10(6) cells, and those with RBCs released 3.69 +/- 0.67 ng/10(6) cells. Control experiments indicated that the effect was not due to platelet contamination of the RBCs and could not be reproduced with RBC supernatants or RBC membrane ghosts. An interesting characteristic of this interaction was that the eosinophils and RBCs had to be in close contact for the enhancement to occur. We also observed that at low calcium concentrations (0.6 mM), the eosinophils had to be primed with fMLP for the RBC effect to occur, but priming was not required at higher calcium concentrations. Several possible mechanisms that would explain the RBC effect on eosinophil LTC4 release were examined: (1) RBCs block the metabolism of LTC4; (2) RBCs protect the eosinophils from oxidative damage; (3) RBCs provide a substrate (or enzyme) that allows increased eosinophil LTC4 production. These mechanisms failed to explain our observation that erythrocytes enhance eosinophil LTC4 release, however, suggesting that alternative mechanisms are responsible for this effect.
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Allergy, Critical Care, and Pulmonary Division, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
D000001:Calcimycin / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000166:cytology / Q000502:physiology*; D006801:Humans; D017997:Leukotriene C4 / Q000097:blood / Q000378:metabolism*; D008863:Microspheres; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011863:Radioimmunoassay; D012685:Sepharose / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
C036210:immunoglobulin G-sepharose; D017997:Leukotriene C4; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012685:Sepharose