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Pathological consequences of leukocytes activation: modulation by lipid mediators

Grant number: 00/05327-8
Support type:Research Projects - Thematic Grants
Duration: November 01, 2000 - May 31, 2006
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Sônia Jancar
Grantee:Sônia Jancar
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):01/14972-7 - Modulation of macrophage tumoricidal activity by lipid mediators and apoptotic cells, BP.DD

Abstract

Cytotoxicity is an important function of polymorphonuclear leukocytes, macrophages and NK cells that can be dramatically increased by bacterial products and/or cytokines produced by T lymphocytes. This characteristic of leukocytes, essential for defense against infections and control of tumor growth, can also determine tissue damage. The limits between these two situations, protection and damage, and the factors that determine the shift from one situation to the other are poorly understood. Lipid mediators are released by leukocytes and are important regulators of these cells and, consequently, of the pathological alterations caused by them. In the project presented here we propose studies on the: 1. pathological consequences of neutrophils activation, focusing on the mechanisms of activation of these cells that lead to tissue damage. Basic aspects of neutrophyl/endothelial cell interactions and factors involved in the activation of these cells will be investigated in experimental models. Clinical studies will also be included; 2) pathological consequences of macrophage activation/inhibition through studies on the mechanisms involved in: a) stimulation of the cytotoxic activity of macrophages by Mycoplasma arthritides superantigen; b) inhibition of macrophage tumoricidal activity by apoptotic cells and its consequences in tumor growth; 3) pathological consequences of eosinophils and lymphocytes activation, through studies of the mechanisms responsible for the migration and activation of these cells, of relevance for the inflammatory alterations found in experimental aliergic asthma. In these studies, particular emphasis will be put on the role of eicosanoids and PAF, and interactions with cytokines and other molecules, in the pathological alterations induced by activated leukocytes. The effect of immune and pharmacological intervention will also be investigated. (AU)

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)
GAMA LANDGRAF‚ R.; JANCAR‚ S.; STEIL‚ AA; SIROIS‚ P. Modulation of allergic and immune complex-induced lung inflammation by bradykinin receptor antagonists. Inflammation Research, v. 53, n. 2, p. 78-83, 2004.
SVENSJÖ‚ E.; BOSCHCOV‚ P.; KETELHUTH‚ DFJ; JANCAR‚ S.; GIDLUND‚ M. Increased microvascular permeability in the hamster cheek pouch induced by oxidized low density lipoprotein (oxLDL) and some fragmented apolipoprotein B proteins. Inflammation Research, v. 52, n. 5, p. 215-220, 2003.

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