Author | Vilela, Márcia Carvalho | |
Author | Lima, Graciela Kunrath | |
Author | Rodrigues, David Henrique | |
Author | Queiroz, Norinne Lacerda | |
Author | Pedroso, Vinicius Sousa Pietra | |
Author | Miranda, Aline Silva de | |
Author | Rachid, Milene Alvarenga | |
Author | Kroon, Erna Geessien | |
Author | Campos, Marco Antônio | |
Author | Teixeira, Mauro Martins | |
Author | Teixeira, Antonio Lucio | |
Access date | 2017-04-12T17:07:45Z | |
Available date | 2017-04-12T17:07:45Z | |
Document date | 2016 | |
Citation | VILELA, Márcia Carvalho et al. Platelet Activating Factor (PAF) Receptor Deletion or Antagonism Attenuates Severe HSV-1 Meningoencephalitis. J Neuroimmune Pharmacol, v. 11, p. 613-621, 2016 | pt_BR |
ISSN | 1557-1890 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/18428 | |
Language | eng | pt_BR |
Publisher | Springer Science + Business Media | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Herpes simplex virus-1 | pt_BR |
Title | Platelet Activating Factor (PAF) Receptor Deletion or Antagonism Attenuates Severe HSV-1 Meningoencephalitis | pt_BR |
Type | Article | |
DOI | 10.1007/s11481-016-9684-7 | |
Abstract | Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The exacerbated immune response against the virus contributes to the disease severity and death. Platelet activating factor (PAF) is a mediatorcapable of inducing increase in vascular perme ability, production of cytokines on endothelial cells and leukocytes. We aimed to investigate the activation of PAF receptor (PAFR) and its contribution to the severity of the inflammatory response in the brain following HSV-1 infection. C57BL/6 wild-type (WT) and PAFR deficient (PAFR−/−) mice were inoculated intracranially with 104 plaque-forming units (PFU) of HSV-1.
Visualization of leukocyte recruitment was performed using intravital microscopy. Cells infiltration in the brain tissue were analyzed by flow cytometry. Brain was removed for chemokine assessment by ELISA and for histopathological analysis. The pharmacological inhibition by the PAFR antagonist UK-74,505 was also analyzed. In PAFR−/−mice, there was delayed lethality but no difference in viral load.
Histopathological analysis of infected PAFR −/−mice showed that brain lesions were less severe when compared to their WT counterparts. Moreover, PAFR −/−mice showed less TCD4 +,TCD8 + and macrophages in brain tissue. This reduction of the presence of leukocytes in parenchyma may be mechanistically explained by a decrease in leukocytes rolling a nd adhesion. PAFR−/−mice also presented a reduction of the chemokine CXC L9 in the brain. In addition, by antagonizing PAFR, survival of C57BL/6 infected mice increased. Altogether, our data suggest that PAFR plays a role in the pathogenesis of experimental HSV-1 meningoencephalitis, and its blockade prevents severe disease manifestation. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório Interdisciplinar de Investigação Médica. Belo Horizonte, MG, Brazil/Universidade Federal de Juiz de Fora. Departamento de Ciências Básicas da Vida. Governador Valadares, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Microbiologia. Belo Horizonte, MG,Brazil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório Interdisciplinar de Investigação Médica. Belo Horizonte, MG, Brazil/Universidade Federal de Juiz de Fora. Departamento de Ciências Básicas da Vida. Governador Valadares, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório Interdisciplinar de Investigação Médica. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório Interdisciplinar de Investigação Médica. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório Interdisciplinar de Investigação Médica. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Morfologia. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório Interdisciplinar de Investigação Médica. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Microbiologia. Belo Horizonte, MG,Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório Interdisciplinar de Investigação Médica. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório Interdisciplinar de Investigação Médica. Belo Horizonte, MG, Brazil | pt_BR |
Subject | Herpes simplex virus-1 | pt_BR |
Subject | Encephalitis | pt_BR |
Subject | PAFR | pt_BR |
Subject | PAFR antagonist “UK74,505” | pt_BR |
Subject | Chemokines | pt_BR |
Embargo date | 2040-01-01 | |