title: Mas receptor deficiency exacerbates lipopolysaccharide-induced cerebral and systemic inflammation in mice.
abstract: Beyond the classical actions of the renin-angiotensin system on the regulation of cardiovascular homeostasis, several studies have shown its involvement in acute and chronic inflammation. The G protein-coupled receptor Mas is a functional binding site for the angiotensin-(1-7); however, its role in the immune system has not been fully elucidated. In this study, we evaluated the effect of genetic deletion of Mas receptor in lipopolysaccharide (LPS)-induced systemic and cerebral inflammation in mice. Inflammatory response was triggered in Mas deficient (Mas(-/-)) and C57BL/6 wild-type (WT) mice (8-12 weeks-old) by intraperitoneal injection of LPS (5 mg/kg). Mas(-/-) mice presented more intense hypothermia compared to WT mice 24 h after LPS injection. Systemically, the bone marrow of Mas(-/-) mice contained a lower number of neutrophils and monocytes 3 h and 24 h after LPS injection, respectively. The plasma levels of inflammatory mediators KC, MCP-1 and IL-10 were higher in Mas(-/-) mice 24 h after LPS injection in comparison to WT. In the brain, Mas(-/-) animals had a significant increase in the number of adherent leukocytes to the brain microvasculature compared to WT mice, as well as, increased number of monocytes and neutrophils recruited to the pia-mater. The elevated number of adherent leukocytes on brain microvasculature in Mas(-/-) mice was associated with increased expression of CD11b - the alpha-subunit of the Mac-1 integrin - in bone marrow neutrophils 3h after LPS injection, and with increased brain levels of chemoattractants KC, MIP-2 and MCP-1, 24 h later. In conclusion, we demonstrated that Mas receptor deficiency results in exacerbated inflammation in LPS-challenged mice, which suggest a potential role for the Mas receptor as a regulator of systemic and brain inflammatory response induced by LPS.
authors: Departamento de Fisiologia e Biofísica, Instituto de Ciência Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Onésia C
authors: OC
authors: Oliveira-Lima
authors: Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Mauro C X
authors: MC
authors: Pinto
authors: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Johan
authors: J
authors: Duchene
authors: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Fatimunnisa
authors: F
authors: Qadri
authors: Departamento de Fisiologia e Biofísica, Instituto de Ciência Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Instituto Sírio-Libanês de Ensino e Pesquisa, São Paulo, Brazil.
authors: Laura L
authors: LL
authors: Souza
authors: Departamento de Fisiologia e Biofísica, Instituto de Ciência Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Natalia
authors: N
authors: Alenina
authors: Departamento de Fisiologia e Biofísica, Instituto de Ciência Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Michael
authors: M
authors: Bader
authors: Departamento de Fisiologia e Biofísica, Instituto de Ciência Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Robson A S
authors: RA
authors: Santos
authors: Departamento de Fisiologia e Biofísica, Instituto de Ciência Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address: julianat@icb.ufmg.br.
authors: Juliana
authors: J
authors: Carvalho-Tavares
mesh_terms: D000818:Animals; D015415:Biomarkers; D001831:Body Temperature; D001835:Body Weight; D001853:Bone Marrow / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002560:Cerebrovascular Circulation; D018925:Chemokines / Q000097:blood / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D007249:Inflammation / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics*
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled
keywords: Inflammation; Lipopolysaccharide; Mas receptor; Renin-angiotensin system