A defect in granulopoiesis in perforin-deficient mice

Abstract

Event Abstract Back to Event A defect in granulopoiesis in perforin-deficient mice Cassio Almeida1*, Maria Ignez Gaspar-Elsas2*, Daniela Masid De Brito1, Lysianne Pinto1, Tulio Queto1, 2, Bruno Vieira1, 2, Thiago Souza2 and Pedro Xavier-Elsas1* 1 UNIVERSIDADE FEDERAL DO RIO DE JANEIRO, Immunology, Brazil 2 fiocruz, Brazil Perforin is a major component in granules of cytotoxic T and Natural Killer lymphocytes, which are active against tumor cells and intracellular pathogens. We previously reported dexamethasone-induced upregulation of eosinophilopoiesis in bone-marrow cultures from different mouse strains, and observed that perforin-deficient bone-marrow lacked this response to dexamethasone. To explore the possible role of perforin in granulopoiesis modulation, we evaluated baseline and glucocorticoid-stimulated counts of total nucleated cells, neutrophils and/or eosinophils in: a) freshly harvested bone-marrow; b) bone-marrow cultured with IL-5 or GM-CSF, with or without dexamethasone. Steady-state bone-marrow cell counts were significantly reduced in perforin-deficient animals compared to wild-type controls. Dexamethasone upregulated IL-5-stimulated eosinophilopoiesis in a dose-dependent-manner in wild-type, but not perforin-deficient mice. In semi-solid cultures, dexamethasone upregulated GM-CSF-stimulated colony formation in wild-type (but not in perforin-deficient) bone-marrow. Intraperitoneal (i.p.) administration of dexamethasone upregulated eosinophilopoiesis and neutrophilopoiesis in wild-type (but not in perforin-deficient) bone-marrow. Dexamethasone induced thymic involution in both mouse strains, confirming that dexamethasone absorption led to similarly active systemic levels. To reconstitute the dexamethasone response in perforin-deficient mice, wild-type T lymphocytes (and their subsets) were transferred from naïve donors into perforin-deficient recipients intravenously, and the latter were subsequently injected with dexamethasone i.p., 24h before bone-marrow harvest and total/differential counts. Total T lymphocytes from wild-type (but not from perforin-deficient) donors reconstituted the response to dexamethasone for both eosinophils and neutrophils in perforin-deficient recipients. Furthermore, neutrophilopoiesis was upregulated when CD4-depleted T lymphocytes were transferred. Together, these data suggest a novel function of perforin in baseline and glucocorticoid-stimulated granulopoiesis. Acknowledgements CNPq, FAPERJ, CAPES. Keywords: Perforin, Hematopoiesis, Eosinophils, Neutrophils, Glucocorticoids Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Almeida C, Gaspar-Elsas M, Masid De Brito D, Pinto L, Queto T, Vieira B, Souza T and Xavier-Elsas P (2013). A defect in granulopoiesis in perforin-deficient mice. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00191 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Cassio Almeida, UNIVERSIDADE FEDERAL DO RIO DE JANEIRO, Immunology, Rio de Janeiro, Brazil, cassiocalmeida@gmail.com Dr. Maria Ignez Gaspar-Elsas, fiocruz, rio de janeiro, Brazil, gasparelsas@gmail.com Dr. Pedro Xavier-Elsas, UNIVERSIDADE FEDERAL DO RIO DE JANEIRO, Immunology, Rio de Janeiro, Brazil, pxelsas@yahoo.com.br Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Cassio Almeida Maria Ignez Gaspar-Elsas Daniela Masid De Brito Lysianne Pinto Tulio Queto Bruno Vieira Thiago Souza Pedro Xavier-Elsas Google Cassio Almeida Maria Ignez Gaspar-Elsas Daniela Masid De Brito Lysianne Pinto Tulio Queto Bruno Vieira Thiago Souza Pedro Xavier-Elsas Google Scholar Cassio Almeida Maria Ignez Gaspar-Elsas Daniela Masid De Brito Lysianne Pinto Tulio Queto Bruno Vieira Thiago Souza Pedro Xavier-Elsas PubMed Cassio Almeida Maria Ignez Gaspar-Elsas Daniela Masid De Brito Lysianne Pinto Tulio Queto Bruno Vieira Thiago Souza Pedro Xavier-Elsas Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.