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ANTI-INFLAMMATORY DRUG EFFECTS ON APOPTOSIS OF EOSINOPHIL GRANULOCYTES DERIVED FROM MURINE BONE-MARROW: CELLULAR MECHANISMS AS RELATED TO LINEAGE, DEVELOPMENTAL STAGE AND HEMOPOIETIC ENVIRONMENT
Affilliation
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Pediatria. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. / Harvard Medical School and Brigham. Departament of Medicine. Boston, MA, USA. / Women`s Hospital. Boston, MA, USA.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. / Harvard Medical School and Brigham. Departament of Medicine. Boston, MA, USA. / Women`s Hospital. Boston, MA, USA.
Abstract
The effects of a variety of widely used anti-inflammatory agents (dexamethasone, indomethacin, and montelu-kast) as well as ubiquitous mediators of inflammation (prostaglandin E
2and nitric oxide) on the development of murine
eosinophils ex vivo and in vivo have been studied over the last decade. The results indicate that developing eosinophils
differ markedly in their responses to these agents from the mature forms of the same lineage, studied either in allergic
human subjects or experimental animal models of allergic disease. Most strikingly, glucocorticoids strongly enhance eosi-nophil development, both in vitroand in vivo. The enhancing effects are also observed during stress reactions and are
strictly dependent on stress-induced glucocorticoid hormone production from the adrenal glands. Some, but not all, of the
developmental effects of glucocorticoids on eosinophils could be accounted for their ability to prevent generation of nitric
oxide through inducible NO synthase, which leads to apoptosis through the CD95-CD95L pathway. A novel mechanism
for the effects of indomethacin in upregulating the development of eosinophils has also been documented. Evidence that
lineage-specific as well as stage-specific cellular response programmes determine these different outcomes is discussed,
along with the perspectives for future research.
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