Myelopoiesis modulation by ACE hyperfunction in kinin B1 receptor knockout mice: Relationship with AcSDKP levels |
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| Authors: | Carlos R. Oliveira Edgar J. Paredes-Gamero Christiano M.V. Barbosa Fábio D. Nascimento Elice C. Batista Felipe C.G. Reis Antonio H.B. Martins Alice T. Ferreira Adriana K. Carmona João B. Pesquero Ivarne L.S. Tersariol Ronaldo C. Araújo Claudia Bincoletto |
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| Affiliation: | 1. Departamento de Farmacologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua 3 de maio, 100, 04040-020 São Paulo, SP, Brazil;2. Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu, 862, 04023-062 São Paulo, SP, Brazil;3. Departamento de Bioquímica, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil;1. Department of Physiopathology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland;2. Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland;1. School of Pharmacy, Nantong University, Nantong 226001, China;2. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong;1. Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Sydney 2006, Australia;2. Biomedical Mass Spectrometry Facility, University of New South Wales, Kensington 2033, Australia;3. Department of Proteomics, School of Biotechnology, Royal Institute of Technology, KTH Science for Life Laboratory, Stockholm, Sweden;4. Institute of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden;1. Health Promotion and Obesity Management Unit, Department of Pathophysiology, Medical Faculty in Katowice, Medical University of Silesia, Katowice, Poland;2. Division of Statistics, Department of Instrumental Analysis, Faculty of Pharmacy and Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland;3. Pathophysiology Unit, Department of Pathophysiology, Medical Faculty in Katowice, Medical University of Silesia, Katowice, Poland;4. International Institute of Molecular and Cell Biology, Warsaw, Poland;5. Department of Arterial Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland;6. Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow, Poland;7. Department of Nephrology, Endocrinology and Metabolic Diseases, Medical Faculty in Katowice, Medical University of Silesia, Katowice, Poland |
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| Abstract: | 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 μM) 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 μg/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?Sca1+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. |
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