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ROLES OF 5-LIPOXYGENASE AND CYSTEINYL-LEUKOTRIENE TYPE 1 RECEPTORS IN THE HEMATOLOGICAL RESPONSE TO ALLERGEN CHALLENGE AND ITS PREVENTION BY DIETHYLCARBAMAZINE IN A MURINE MODEL OF ASTHMA
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Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Departamento de Pediatria. Rio de Janeito, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Departamento de Pediatria. Rio de Janeito, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Departamento de Pediatria. Rio de Janeito, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Departamento de Pediatria. Rio de Janeito, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.
Abstract
Diethylcarbamazine (DEC), which blocks leukotriene production, abolishes the challenge-induced increase in eosinopoiesis
in bone-marrow from ovalbumin- (OVA-) sensitized mice, suggesting that 5-lipoxygenase (5-LO) products contribute to the
hematological responses in experimental asthma models. We explored the relationship between 5-LO, central and peripheral
eosinophilia, and effectiveness of DEC, using PAS or BALB/cmice and 5-LO-deficient mutants. We quantified eosinophil numbers
in freshly harvested or cultured bone-marrow, peritoneal lavage fluid, and spleen, with or without administration of leukotriene
generation inhibitors (DEC and MK886) and cisteinyl-leukotriene type I receptor antagonist (montelukast). The increase in
eosinophil numbers in bone-marrow, observed in sensitized/challenged wild-type mice, was abolished by MK886 and DEC
pretreatment. InALOXmutants, by contrast, therewas no increase inbone-marroweosinophil counts, nor ineosinophil production
in culture, in response to sensitization/challenge. In sensitized/challengedALOX mice, challenge-inducedmigration of eosinophils
to the peritoneal cavity was significantly reduced relative to the wild-type PAS controls. DEC was ineffective in ALOX mice, as
expected from a mechanism of action dependent on 5-LO. In BALB/c mice, challenge significantly increased spleen eosinophil
numbers andDECtreatment prevented this increase.Overall, 5-LOappears as indispensable to the systemichematological response
to allergen challenge, as well as to the effectiveness of DEC
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