Neutrophil-Derived Cytosolic PLA2α Contributes to Bacterial-Induced Neutrophil Transepithelial Migration.

Autor:	Yonker LM; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Pazos MA; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Lanter BB; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Mou H; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115.; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114., Chu KK; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114.; Department of Pathology, Harvard Medical School, Boston, MA 02115., Eaton AD; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114., Bonventre JV; Department of Medicine, Harvard Medical School, Boston, MA 02115.; Renal Division, Brigham and Women's Hospital, Boston, MA 02115; and.; Biomedical Engineering Division, Brigham and Women's Hospital, Boston, MA 02115., Tearney GJ; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114.; Department of Pathology, Harvard Medical School, Boston, MA 02115., Rajagopal J; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114.; Department of Medicine, Harvard Medical School, Boston, MA 02115., Hurley BP; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114; bphurley@mgh.harvard.edu.; Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2017 Oct 15; Vol. 199 (8), pp. 2873-2884. Date of Electronic Publication: 2017 Sep 08.
DOI:	10.4049/jimmunol.1700539
Abstrakt:	Eicosanoids are a group of bioactive lipids that are shown to be important mediators of neutrophilic inflammation; selective targeting of their function confers therapeutic benefit in a number of diseases. Neutrophilic airway diseases, including cystic fibrosis, are characterized by excessive neutrophil infiltration into the airspace. Understanding the role of eicosanoids in this process may reveal novel therapeutic targets. The eicosanoid hepoxilin A3 is a pathogen-elicited epithelial-produced neutrophil chemoattractant that directs transepithelial migration in response to infection. Following hepoxilin A3-driven transepithelial migration, neutrophil chemotaxis is amplified through neutrophil production of a second eicosanoid, leukotriene B4 (LTB4). The rate-limiting step of eicosanoid generation is the liberation of arachidonic acid by phospholipase A2, and the cytosolic phospholipase A2 (cPLA2)α isoform has been specifically shown to direct LTB4 synthesis in certain contexts. Whether cPLA2α is directly responsible for neutrophil synthesis of LTB4 in the context of Pseudomonas aeruginosa- induced neutrophil transepithelial migration has not been explored. Human and mouse neutrophil - epithelial cocultures were used to evaluate the role of neutrophil-derived cPLA2α in infection-induced transepithelial signaling by pharmacological and genetic approaches. Primary human airway basal stem cell - derived epithelial cultures and micro-optical coherence tomography, a new imaging modality that captures two- and three-dimensional real-time dynamics of neutrophil transepithelial migration, were applied. Evidence from these studies suggests that cPLA2α expressed by neutrophils, but not epithelial cells, plays a significant role in infection-induced neutrophil transepithelial migration by mediating LTB4 synthesis during migration, which serves to amplify the magnitude of neutrophil recruitment in response to epithelial infection. (Copyright © 2017 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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