title: Role of endothelins on lymphocyte accumulation in allergic pleurisy.
abstract: Endothelins participate in different aspects of inflammatory reactions, including edema formation and eosinophil accumulation in allergic reaction. In this study, we demonstrated a role for endogenous endothelins in eosinophil and T lymphocyte recruitment and cytokine secretion in a murine model of allergic inflammation. Intrathoracic stimulation with endothelin-1 triggered a neutrophil accumulation at 4 h, concomitant with an increase of CD4+ and CD8+ T lymphocyte populations. Antigen challenge in sensitized animals leads to an increase in eosinophil and mononuclear cell numbers at 24 h. Treatment with ETA receptor antagonist (BQ123) inhibited antigen-induced eosinophil and mononuclear cell migration, whereas the selective ETB receptor antagonist BQ-788 was ineffective. The latter effect of BQ-123 was due to inhibition of CD4+ and CD8+ T lymphocytes. Treatment with BQ-123 also inhibited interleukin-5 levels in the exudate and plasma as well as intracellular staining of interleukin-4, interleukin-5, and interferon-gamma in CD4+ lymphocytes. These findings suggest that endogenous endothelins contribute to allergic inflammation by modulating lymphocyte recruitment and cytokine production.
authors.affiliation: Laboratory of Applied Pharmacology, FarManguinhos, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Sampaio
authors.forename: G A
authors.initials: GA
authors.lastname: Rae
authors.forename: M M
authors.initials: MM
authors.lastname: Henriques
mesh_terms: D000818:Animals; D000077300:Bosentan; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D002634:Chemotaxis, Leukocyte; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D015759:Ionomycin / Q000494:pharmacology; D016131:Lymphocyte Subsets / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008985:Monensin / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010998:Pleurisy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D015848:Interleukin-5; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D013449:Sulfonamides; D015847:Interleukin-4; C086539:BQ 788; D015759:Ionomycin; D007371:Interferon-gamma; D010047:Ovalbumin; D008985:Monensin; D013755:Tetradecanoylphorbol Acetate; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)