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INTERACTION BETWEEN SCAVENGER RECEPTOR CD36 AND PAF RECEPTOR IN MACROPHAGES: LOCATION AND COMMON SIGNALING PATHWAYS.

Grant number: 09/05290-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2009
Effective date (End): March 31, 2013
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Sônia Jancar
Grantee:Francisco José Oliveira Rios
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:06/03982-5 - Molecular aspects involved in leukocytes microbicidal and inflammatory activities in the lung, AP.TEM

Abstract

Macrophages interact with molecular patterns present in microorganisms by a group of receptors (PRR), which are included TLR, dectin and Nod receptors. These cells also interact with molecular patterns present in modified lipoproteins and apoptotic cells through scavenger receptors (eg. SRA and CD36). Such interactions may induce macrophage polarization to M1, responsible for defense against infection or for a M2 suppressor phenotype, involved in homeostasis and tissue remodeling. Macrophages also express receptors for lipid mediators, such as prostaglandins, leukotrienes and PAF. There is evidence that receptors for lipid mediators interfere with the signaling triggered by phagocytic receptors, favoring the M1 macrophage phenotype. However, interaction of receptors for lipid mediators with scavenger receptors is poorly understood. There is evidence that PAF-R and CD36 receptor share common ligands, and that the activation of these receptors induces similar responses. CD36 is a receptor involved in phagocytosis of apoptotic cells leading macrophages to a suppressor phenotype. Results from our laboratory have shown that this effect is dependent on PAF-R. We have also shown that PAF-R and scavenger receptors have a function in macrophages suppressor phenotype in the tumor environment favoring the tumor growth. The objective of this project is to investigate the molecular mechanisms involved in activation of CD36 receptor and PAF-R in macrophages, alone or in combination, focusing on the cellular localization and the signaling pathways activated. Moreover, considering the recent evidence that the location of receptors in a common compartment (lipid rafts) favors the interactions between them, we will investigate whether the CD36 and PAF-R are located in the same lipid raft microdomains in basal conditions or if it is dependent on macrophage polarization to the M2 phenotype. The elucidation of mechanisms these mechanisms involved may be relevant to establishment of new therapeutic strategies for the control of tumor growth as well as vascular inflammation in atherosclerosis.

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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)
RIOS, FRANCISCO J. O.; KOGA, MARIANA M.; FERRACINI, MATHEUS; JANCAR, SONIA. Co-Stimulation of PAFR and CD36 Is Required for oxLDL-Induced Human Macrophages Activation. PLoS One, v. 7, n. 5, p. e36632, 2012. Web of Science Citations: 26.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.