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Study of vascular permeability in endothelial cells regarding Plamodium berghei NK65

Grant number: 17/00077-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2017
Effective date (End): November 30, 2017
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Sabrina Epiphanio
Grantee:Gabriel Cândido Moura
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malaria is an infectious parasitic disease considered a public health problem and represents a risk to the most diverse populations. Present in 104 countries, considered as endemic areas, this disease puts at risk 40% of the world population. Infections by Plasmodium spp. can lead to a serious respiratory condition, with pulmonary complications called acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This syndrome is characterized by acute inflammation, injury of the alveolar endothelium and pulmonary parenchyma, dysfunction and increased permeability of the pulmonary alveolar-capillary barrier and consequent formation of oedema. The large number of potentially involved factors, associated with the great difficulties in the study of the disease in humans, causes the molecular basis of this pulmonary dysfunction to remain poorly understood, leading to a high mortality in health units. Recent studies have demonstrated that different components of the immune response are involved in the pathogenesis of malaria-associated ALI/ARDS, and both host and parasite factors have important roles in the development of the disease. Murine models, used in ALI/ARDS research, have demonstrated the involvement of the essential of neutrophils, various cytokines, and chemokines in the process of increasing vascular permeability. Mechanisms of regulation of endothelial cell permeability involving dynamic interactions and structural alterations of cytoskeletal components play a critical role in the modulation of the inflammatory response and maintenance of the pulmonary endothelium. Thus, due to the lack of knowledge of the determinants of the pathogenesis of malaria-associated ALI/ARDS, this project intends to analyze vasculature permeability, especially in co-cultures of pulmonary endothelial cells and erythrocytes. The future development of drugs that modulate this alveolar-capillary barrier may be essential for improving the prognosis of the disease. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ORTOLAN, LUANA DOS SANTOS; SERCUNDES, MICHELLE KLEIN; MOURA, GABRIEL CANDIDO; QUIRINO, THATYANE DE CASTRO; DEBONE, DANIELA; COSTA, DOUGLAS DE SOUSA; MURILLO, OSCAR; FARIAS MARINHO, CLAUDIO ROMERO; EPIPHANIO, SABRINA. Endothelial Protein C Receptor Could Contribute to Experimental Malaria-Associated Acute Respiratory Distress Syndrome. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2019, . (14/20451-0, 13/20718-3, 13/00981-1, 17/05782-8, 17/00077-4)

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