Augmentation of LTC(4) synthesis in human eosinophils caused by CD3-stimulated Th2-like cells in vitro.
We assessed the effect of anti-CD3-stimulated secretion of cultured human Th1- and Th2-like cells on leukotriene C(4) (LTC(4)) secretion in isolated human eosinophils. T helper (Th) cell subsets were generated from human naive CD4(+) T cells cocultured with irradiated human transformed B cells and either recombinant human interleukin (rhIL)-1beta plus rhIL-6 plus rhIL-12 for Th1-like cells or rhIL-1beta plus rhIL-6 plus rhIL-4 for Th2-like cells. Coincubation of eosinophils with 1:5 dilution of Th2-supernatant (Sup) caused an increase in LTC(4) secretion caused by 0.1 microM formyl-Met-Leu-Phe and 5 microg/ml cytochalasin B from 921 +/- 238 to 3,067 +/- 1,462 pg/10(6) eosinophils (P < 0.01). Th1-Sup at the same dilution had no augmenting effect on stimulated secretion of LTC(4) in eosinophils despite substantial concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the supernatant. Dilution of Th1-Sup caused increased LTC(4) that returned to baseline after immunoabsorption of GM-CSF, suggesting the presence of a possible inhibitory factor. We demonstrate that pretreatment of eosinophils with 1:5 dilution of Th2-Sup but not of Th1-Sup causes substantial augmentation of LTC(4) secretion in vitro and establishes that human Th2 cells cause direct augmentation of LTC(4) secretion within 15-30 min of exposure.
Muñoz
N M
NM
Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Illinois 60637, USA.
van Seventer
G A
GA
Semnani
R T
RT
Leff
A R
AR
D015415:Biomarkers; D017252:CD3 Complex / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology; D004804:Eosinophils / Q000378:metabolism / Q000502:physiology; D006801:Humans; D017997:Leukotriene C4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology
D015415:Biomarkers; D017252:CD3 Complex; D016207:Cytokines; D017997:Leukotriene C4