Cytoadhesion in the immunopathogenesis of malaria-associated acute respiratory distress syndrome.

Author(s)

Luana dos Santos Ortolan

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2017-12-13

Examining board members

Sabrina Epiphanio; Daniel Youssef Bargieri; Marcos Leoni Gazarini Dutra; Wothan Tavares de Lima; Carla Máximo Prado

• Advisor: Sabrina Epiphanio; Claudio Romero Farias Marinho

Abstract

Infections by Plasmodium sp. can lead to pulmonary complications called acute respiratory distress syndrome (ARDS). The experimental model, using the murine parasite Plasmodium berghei ANKA (PbA) and DBA/2 mice, is used no study of immunological mediators and factors that allow the establishment of lung lesions. DBA / 2 mice infected with PbA were classified according to cause of death as ARDS or HP (hyperparasitism). In vivo the parasite distribution was analyzed, and the lungs were collected for respiratory capacity analysis, histopathology, vascular permeability, qRT-PCR, immunohistochemistry and anti-inflammatory effect (Dexamethasone-Dexa). In vitro, pulmonary endothelial cells were submitted to various stimuli. We found that there is accumulation of PbA in the lungs of DBA/2 with ARDS and TNF and IFN-γ increase cytoadhesion, expression of ICAM-1, VCAM-1 and EPCR. Inhibition of TNF decreases adhesion and dexa protects animals by decreasing inflammatory factors, EPCR and inhibiting the opening of interendothelial junctions. The intervention of cytoadherence and vascular permeability with the use of corticosteroids may be an important target for the treatment and prevention of ARDS. (AU)

• FAPESP's process: 13/20718-3 - The role of cytoadherence and Toll-like receptors (TLRs) in the immunopathogenesis of murine severe malaria associated to acute respiratory distress syndrome
• Grantee: Luana dos Santos Ortolan
• Support type: Scholarships in Brazil - Doctorate