title: Absence of calcium-independent phospholipase A2 β impairs platelet-activating factor production and inflammatory cell recruitment in Trypanosoma cruzi-infected endothelial cells.
abstract: Both acute and chronic phases of Trypanosoma cruzi (T. cruzi) infection are characterized by tissue inflammation, mainly in the heart. A key step in the inflammatory process is the transmigration of inflammatory cells across the endothelium to underlying infected tissues. We observed increased arachidonic acid release and platelet-activating factor (PAF) production in human coronary artery endothelial cells (HCAEC) at up to 96 h of T. cruzi infection. Arachidonic acid release is mediated by activation of the calcium-independent phospholipase A2 (iPLA2) isoforms iPLA2 β and iPLA2 γ, whereas PAF production was dependent upon iPLA2 β activation alone. Trypanosoma cruzi infection also resulted in increased cell surface expression of adhesion molecules. Increased adherence of inflammatory cells to T. cruzi-infected endothelium was blocked by inhibition of endothelial cell iPLA2 β or by blocking the PAF receptor on inflammatory cells. This suggests that PAF, in combination with adhesion molecules, might contribute to parasite clearing in the heart by recruiting inflammatory cells to the endothelium.
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, 1402 S. Grand BlvdSt Louis, 63104, Missouri.
authors.forename: Janhavi
authors.initials: J
authors.lastname: Sharma
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Saint Louis University School of Medicine, 1402 S. Grand Blvd., St Louis, 63104, Missouri.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Eickhoff
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Saint Louis University School of Medicine, 1402 S. Grand Blvd., St Louis, 63104, Missouri.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, 1402 S. Grand BlvdSt Louis, 63104, Missouri.
authors.forename: John O
authors.initials: JO
authors.lastname: Marentette
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, Washington University in St. Louis, St. Louis, 63110, Missouri.
authors.forename: John
authors.initials: J
authors.lastname: Turk
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, 1402 S. Grand BlvdSt Louis, 63104, Missouri.
authors.forename: Jane
authors.initials: J
authors.lastname: McHowat
keywords: Inflammation; endothelial; phospholipase A2; platelet‐activating factor
references.citation: J Parasitol. 2010 Aug;96(4):758-64
references.pmid: 20738200
references.citation: Can J Biochem Physiol. 1959 Aug;37(8):911-7
references.pmid: 13671378
references.citation: Am J Trop Med Hyg. 1990 Sep;43(3):274-81
references.pmid: 2121055
references.citation: Clin Infect Dis. 2009 Sep 1;49(5):e52-4
references.pmid: 19640226
references.citation: Am J Trop Med Hyg. 1993 Mar;48(3):348-57
references.pmid: 8470772
references.citation: Clin Cardiol. 2000 Dec;23(12):883-9
references.pmid: 11129673
references.citation: J Immunol. 2004 Jul 1;173(1):463-70
references.pmid: 15210806
references.citation: Am J Physiol Cell Physiol. 2011 Apr;300(4):C872-9
references.pmid: 21191104
references.citation: Biochem Pharmacol. 1992 Sep 25;44(6):1001-8
references.pmid: 1329754
references.citation: J Biol Chem. 2002 Sep 6;277(36):32807-14
references.pmid: 12089145
references.citation: Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):727-33
references.pmid: 12006383
references.citation: N Engl J Med. 2011 Jun 30;364(26):2527-34
references.pmid: 21714649
references.citation: Physiol Rev. 2000 Oct;80(4):1669-99
references.pmid: 11015622
references.citation: Parasitol Res. 2013 Jul;112(7):2731-9
references.pmid: 23681190
references.citation: Am J Physiol. 1998 Dec;275(6):C1498-507
references.pmid: 9843711
references.citation: J Investig Med. 2001 Jan;49(1):104-11
references.pmid: 11217139
references.citation: Biochim Biophys Acta. 2000 Oct 31;1488(1-2):1-19
references.pmid: 11080672
references.citation: Am J Pathol. 1984 Feb;114(2):209-16
references.pmid: 6230012
references.citation: Thromb Res. 2007;120(4):597-605
references.pmid: 17188740
references.citation: Biochemistry. 2001 Dec 11;40(49):14921-31
references.pmid: 11732912
references.citation: Ann Trop Med Parasitol. 2008 Sep;102(6):481-7
references.pmid: 18782487
references.citation: Chem Rev. 2011 Oct 12;111(10):6130-85
references.pmid: 21910409
references.citation: Infect Immun. 1999 Jan;67(1):308-18
references.pmid: 9864231
references.citation: Am J Physiol Cell Physiol. 2007 Nov;293(5):C1467-71
references.pmid: 17728394
references.citation: Infect Immun. 1999 Oct;67(10):5434-40
references.pmid: 10496926
references.citation: Cardiovasc Drugs Ther. 2009 Feb;23(1):49-59
references.pmid: 18931897