Abstract 13469: Absence of Calcium-Independent Phospholipase A2beta Does Not Affect Recruitment but Impairs Function of Inflammatory Cells in T. Cruzi-Induced Myocarditis
Both acute and chronic phases of T. cruzi infection are characterized by myocardial inflammation. A key step in the inflammatory process is the transmigration of inflammatory cells across the endothelium and into underlying infected tissues. In in vitro studies, we observed an upregulation of surface adhesion molecules and a calcium-independent phospholipase A2-β (iPLA2β)-mediated increase in platelet activating factor (PAF) production in coronary endothelial cells infected with T. cruzi. A corresponding increase in inflammatory cell adherence to the endothelium was also observed. This suggests that the combination of endothelial cell surface expression of adhesion molecules and increased PAF production might contribute to parasite clearing in the heart by recruiting inflammatory cells. We infected wild type (WT) and iPLA2β-knockout (iPLA2β-KO) mice with T. cruzi (Brazil strain, 5000 parasites, i.p. injection) and determined myocardial inflammation and parasite accumulation at 4, 8 and 12 weeks. We did not observe any difference in inflammatory cell accumulation between WT and KO mice. Also no difference in ECG recordings at baseline, 4 and 8 weeks was observed. However, a significant increase in parasite pseudocysts was recorded in the hearts of iPLA2β-KO mice. Macrophages, predominantly observed in inflammatory lesions in Chagasic hearts, are vital in parasite clearing via the release of nitric oxide (NO). We determined that macrophages deficient in iPLA2β are unable to produce normal levels of NO in response to T. cruzi in vitro, suggesting that macrophages in iPLA2β-KO mice are unable to clear parasites in infected tissues. Thus, the absence of iPLA2β may not influence inflammatory cell recruitment to the myocardium but may impair the function of these cells to clear the parasite after acute infection.
- © 2011 by American Heart Association, Inc.