monensin and Pleurisy

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.

Topics: Animals; Bosentan; CD4-Positive T-Lymphocytes; Chemotaxis, Leukocyte; Endothelin Receptor Antagonists; Endothelin-1; Humans; Interferon-gamma; Interleukin-4; Interleukin-5; Ionomycin; Lymphocyte Subsets; Male; Mice; Mice, Inbred C57BL; Monensin; Oligopeptides; Ovalbumin; Peptides, Cyclic; Piperidines; Pleurisy; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin; Respiratory Hypersensitivity; Sulfonamides; Tetradecanoylphorbol Acetate