title: The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors.
abstract: Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp-) deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.
authors.forename: Pedro
authors.identifier: 0000-0003-3057-6062
authors.initials: P
authors.lastname: Xavier-Elsas
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.
authors.forename: Cássio Luiz Coutinho Almeida
authors.identifier: 0000-0001-9173-7208
authors.initials: CL
authors.lastname: da Silva
authors.affiliation: Departamento de Pediatria, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, FIOCRUZ, 22250-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Bruno Marques
authors.initials: BM
authors.lastname: Vieira
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Masid-de-Brito
authors.affiliation: Departamento de Pediatria, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, FIOCRUZ, 22250-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Túlio
authors.initials: T
authors.lastname: Queto
authors.affiliation: Departamento de Pediatria, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, FIOCRUZ, 22250-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: de Luca
authors.affiliation: Departamento de Pediatria, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, FIOCRUZ, 22250-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Thiago Soares de Souza
authors.initials: TS
authors.lastname: Vieira
authors.affiliation: Departamento de Pediatria, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, FIOCRUZ, 22250-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Maria Ignez C
authors.identifier: 0000-0003-0883-8652
authors.initials: MI
authors.lastname: Gaspar-Elsas
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D052899:Pore Forming Cytotoxic Proteins; C483886:perforin, mouse; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor