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Hepoxilin A 3 is a key driver of neutrophil migration in a model of acute P. aeruginosa infection.
Author(s) -
Pazos Michael A,
Hurley Bryan P
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1215.4
Subject(s) - chemotaxis , bronchoalveolar lavage , pseudomonas aeruginosa , immunology , neutrophil extracellular traps , infiltration (hvac) , in vivo , inflammation , cystic fibrosis , lung , eicosanoid , microbiology and biotechnology , biology , receptor , medicine , enzyme , bacteria , biochemistry , genetics , physics , arachidonic acid , thermodynamics
Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states including acute bacterial pneumonia, cystic fibrosis, ARDS, as well as several others. Hepoxilin A 3 (HXA3) is a chemotactic eicosanoid shown in vitro to mediate the transepithelial passage of neutrophils. Using a murine model of acute infection with Pseudomonas aeruginosa , we demonstrate HXA3 plays a significant role in transepithelial migration of neutrophils in vivo. Here we present data that modulation of HXA3 signaling during bacterial lung infection of mice significantly reduces neutrophil accumulation in the airspace. Using bronchoalveolar lavage, we measure the numbers of neutrophils and quantify lipid‐associated chemotactic bioactivity within the airspace. We target HXA3 through inhibition of the HXA3 biosynthetic pathway, enzymatic degradation of HXA3 chemotactic potential, and competitive inhibition. We conclude that modulation of HXA3 signaling represents a viable therapeutic target for the prevention of neutrophil infiltration and subsequent immunopathology.