Long-term exacerbation by interleukin 13 of IgE-mediated eosinophilia in rats.
Recent work shows that at least two cycles of antigen challenge applied in a 7-day interval are required to yield tissue eosinophil accumulation in IgE-passively sensitized rats. Since interleukin (IL)-13 is widely regarded as a key mediator in eosinophilic responses associated with mast cells and IgE, we investigated whether this cytokine could replace the first cycle of sensitization and challenge in its proeosinophilic role. We found that IL-13 (25 and 50 ng/cavity) injected into the rat pleural space led to eotaxin generation and a dose-dependent accumulation of eosinophils following IgE-passive sensitization and challenge 7 days later. IL-13 failed to cause eosinophil chemotaxis in vitro but induced eosinophil accumulation into the pleural cavity of naïve rats, which peaked 1 day and faded 72 h post-challenge. No changes were found 1 week after intrapleural injection of IL-13, except an approximately 40-50% increase in the number of adhered and non-adhered pleural mast cells. As recovered from the pleural effluent 1 week after IL-13, mast cells expressed the same amount of IgE bound on their surface as compared to controls. However, they generated 3-fold more LTC(4) following IgE-sensitization and challenge in vitro, keeping intact the amount of histamine released. Finally, pretreatment with zileuton (50 microg/cavity) 1 h before allergen challenge prevented eosinophil accumulation in those animals injected with IL-13 1 week before. In conclusion, our findings show that IL-13 causes a long-term exacerbation of the IgE-mediated eosinophilic response in a mechanism associated with heightened cysteinyl-leukotriene (cys-LT) production by resident mast cells.
Rossi
Maria Inês Doria
MI
Department of Physiology and Pharmacodynamics, Laboratory of Inflammation, IOC/Fiocruz Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, Brazil.
de Oliveira Barreto
Emiliano
E
Pires
Ana Lúcia Aguiar
AL
Rossi
Maria Isabel Doria
MI
Dias
Vanessa Aparecida Ribeiro
VA
Cordeiro
Renato Sérgio Balão
RS
Martins
Marco Aurélio
MA
Lima
Marcia Coronha Ramos
MC
D000818:Animals; D002465:Cell Movement; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000096:biosynthesis; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000633:toxicity*; D017997:Leukotriene C4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D008407:Mast Cells / Q000166:cytology / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
C515458:Ccl11 protein, rat; D054413:Chemokine CCL11; D019742:Chemokines, CC; D018793:Interleukin-13; D016859:Lipoxygenase Inhibitors; D017997:Leukotriene C4; D007073:Immunoglobulin E