Myelopoiesis modulation by ACE hyperfunction in kinin B-1 receptor knockout mice: Relationship with AcSDKP levels

Myelopoiesis modulation by ACE hyperfunction in kinin B-1 receptor knockout mice: Relationship with AcSDKP levels

Autor Oliveira, Carlos R. Autor UNIFESP Google Scholar
Paredes-Gamero, Edgar J. Autor UNIFESP Google Scholar
Barbosa, Christiano M. V. Autor UNIFESP Google Scholar
Nascimento, Fabio D. Autor UNIFESP Google Scholar
Batista, Elice C. Autor UNIFESP Google Scholar
Reis, Felipe C. G. Autor UNIFESP Google Scholar
Martins, Antonio H. B. Autor UNIFESP Google Scholar
Ferreira, Alice T. Autor UNIFESP Google Scholar
Carmona, Adriana K. Autor UNIFESP Google Scholar
Pesquero, Joao B. Autor UNIFESP Google Scholar
Tersariol, Ivarne L. S. Autor UNIFESP Google Scholar
Araujo, Ronaldo C. Autor UNIFESP Google Scholar
Bincoletto, Claudia Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo Angiotensin I-converting enzyme (ACE), a common element of renin-angiotensin system (RAS) and kallikrein-kinin system (KKS), is involved in myelopoiesis modulation, mainly by cleaving the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP). Based on this finding and in our results showing B1 and B2 kinin receptors expression in murine bone marrow (BM) cells, we evaluated the ACE influence on myelopoiesis of kinin B1 receptor knockout mice (B1KO) using long-term bone marrow cultures (LTBMCs). Captopril and AcSDKP were used as controls. Enhanced ACE activity, expressed by non-hematopoietic cells (Ter-199(-) and CD45(-)), was observed in B1KO LTBMCs when compared to wild-type (WT) cells. ACE hyperfunction in B1KO cells was maintained when LTBMCs from B1KO mice were treated with captopril (1.0 mu M) or AcSDKP (1.0 nM). Although no alterations were observed in ACE mRNA and protein levels under these culture conditions, 3.0 nM of AcSDKP increased ACE mRNA levels in WT LTBMCs. No alteration in the number of GM-CFC was seen in B1KO mice compared to WT animals, even when the former were treated with AcSDKP (10 mu g/kg) or captopril (100 mg/kg) for 4 consecutive days. Hematological data also revealed no differences between WT and B1KO mice under basal conditions. When the animals received 4 doses of lipopolysaccharide (LPS), a decreased number of blood cells was detected in B1KO mice in relation to WT. We also found a decreased percentage of Gr1(+)/Mac-1(+), Ter119(+), B220(+), CD3(+), and Lin(-)Sca-1(+)c-Kit(+) (LSK) cells in the BM of B1KO mice compared to WT animals. Low AcSDKP levels were observed in BM cultures from B1KO in comparison to WT cultures. We conclude that ACE hyperfunction in B1KO mice resulted in faster hydrolysis of AcSDKP peptide, which in turn decreased in BM tissues allowing HSC to enter the S stage of the cell cycle. (C) 2010 Elsevier Ireland Ltd. All rights reserved,
Palavra-chave ACE hyperfunction
BK
Bone marrow
B1KO mice
GM-CFC
AcSDKP levels
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento FAPESP: 06/57253-4
Data de publicação 2010-03-30
Publicado em Chemico-biological Interactions. Clare: Elsevier B.V., v. 184, n. 3, p. 388-395, 2010.
ISSN 0009-2797 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 388-395
Fonte http://dx.doi.org/10.1016/j.cbi.2010.01.015
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000276920400010
Endereço permanente http://repositorio.unifesp.br/handle/11600/32385

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