title: Mice with Genetic Deletion of Group VIA Phospholipase A2β Exhibit Impaired Macrophage Function and Increased Parasite Load in Trypanosoma cruzi-Induced Myocarditis.
abstract: Trypanosoma cruzi infection, which is the etiological agent of Chagas disease, is associated with intense inflammation during the acute and chronic phases. The pathological progression of Chagas disease is influenced by the infiltration and transmigration of inflammatory cells across the endothelium to infected tissues, which are carefully regulated processes involving several molecular mediators, including adhesion molecules and platelet-activating factor (PAF). We have shown that PAF production is dependent upon calcium-independent group VIA phospholipase A2β (iPLA2β) following infection of human coronary artery endothelial cells (HCAECs) with T. cruzi, suggesting that the absence of iPLA2β may decrease the recruitment of inflammatory cells to the heart to manage parasite accumulation. Cardiac endothelial cells isolated from iPLA2β-knockout (iPLA2β-KO) mice infected withT. cruzi demonstrated decreased PAF production compared to that by cells isolated from wild-type (WT) mice but demonstrated increases in adhesion molecule expression similar to those seen in WT mice. Myocardial inflammation in iPLA2β-KO mice infected with T. cruzi was similar in severity to that in WT mice, but the iPLA2β-KO mouse myocardium contained more parasite pseudocysts. Upon activation, macrophages from iPLA2β-KO mice produced significantly less nitric oxide (NO) and caused lessT. cruzi inhibition than macrophages from wild-type mice. Thus, the absence of iPLA2β activity does not influence myocardial inflammation, but iPLA2β is essential forT. cruzi clearance.
authors: Department of Pathology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
authors: Janhavi
authors: J
authors: Sharma
authors: Division of Infectious Diseases, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
authors: Jennifer R
authors: JR
authors: Blase
authors: Division of Infectious Diseases, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
authors: Daniel F
authors: DF
authors: Hoft
authors: Department of Pathology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
authors: John O
authors: JO
authors: Marentette
authors: Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
authors: John
authors: J
authors: Turk
authors: Department of Pathology, Saint Louis University School of Medicine, St. Louis, Missouri, USA mchowaj@slu.edu.
authors: Jane
authors: J
authors: McHowat
mesh_terms: D000818:Animals; D002460:Cell Line; D002598:Chagas Cardiomyopathy / Q000378:metabolism* / Q000469:parasitology*; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D054522:Group VI Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009573:Nitrites; D059208:Parasite Load
chemical_list: D009573:Nitrites; D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse