title: Pathogen induced chemo-attractant hepoxilin A3 drives neutrophils, but not eosinophils across epithelial barriers.
abstract: Pathogen induced migration of neutrophils across mucosal epithelial barriers requires epithelial production of the chemotactic lipid mediator, hepoxilin A3 (HXA3). HXA3 is an eicosanoid derived from arachidonic acid. Although eosinophils are also capable of penetrating mucosal surfaces, eosinophilic infiltration occurs mainly during allergic processes whereas neutrophils dominate mucosal infection. Both neutrophils and eosinophils can respond to chemotactic gradients of certain eicosanoids, however, it is not known whether eosinophils respond to pathogen induced lipid mediators such as HXA3. In this study, neutrophils and eosinophils were isolated from human blood and placed on the basolateral side of polarized epithelial monolayers grown on permeable Transwell filters and challenged by various chemotactic gradients of distinct lipid mediators. We observed that both cell populations migrated across epithelial monolayers in response to a leukotriene B4 (LTB4) gradient, whereas only eosinophils migrated toward a prostaglandin D2 (PGD2) gradient. Interestingly, while pathogen induced neutrophil trans-epithelial migration was substantial, pathogen induced eosinophil trans-epithelial migration was not observed. Further, gradients of chemotactic lipids derived from pathogen infected epithelial cells known to be enriched for HXA3 as well as purified HXA3 drove significant numbers of neutrophils across epithelial barriers, whereas eosinophils failed to respond to these gradients. These data suggest that although the eicosanoid HXA3 serves as an important neutrophil chemo-attractant at mucosal surfaces during pathogenic infection, HXA3 does not appear to exhibit chemotactic activity toward eosinophils.
authors: Department of Pediatrics, Harvard Medical School, Boston, MA 02115, United States; Center for Immunology and Inflammatory Diseases and the Food Allergy Center, Massachusetts General Hospital, Charlestown, MA 02129, United States.
authors: S A
authors: SA
authors: Kubala
authors: Center for Immunology and Inflammatory Diseases and the Food Allergy Center, Massachusetts General Hospital, Charlestown, MA 02129, United States.
authors: S U
authors: SU
authors: Patil
authors: Department of Pediatrics, Harvard Medical School, Boston, MA 02115, United States; Center for Immunology and Inflammatory Diseases and the Food Allergy Center, Massachusetts General Hospital, Charlestown, MA 02129, United States.
authors: W G
authors: WG
authors: Shreffler
authors: Department of Pediatrics, Harvard Medical School, Boston, MA 02115, United States; Mucosal Immunology & Biology Research Center, Massachusetts General Hospital, Charlestown, MA 02129, United States. Electronic address: bphurley@partners.org.
authors: B P
authors: BP
authors: Hurley
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002460:Cell Line; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D004804:Eosinophils / Q000276:immunology*; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D057705:Transendothelial and Transepithelial Migration
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D016209:Interleukin-8; D007975:Leukotriene B4; C038243:8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid; D009195:Peroxidase; D015126:8,11,14-Eicosatrienoic Acid
keywords: Eicosanoids; Eosinophils; Hepoxilin A3; Leukotriene B4; Neutrophils; Prostaglandin D2