A defect in granulopoiesis in perforin-deficient mice
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1
UNIVERSIDADE FEDERAL DO RIO DE JANEIRO, Immunology, Brazil
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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.
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
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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