Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration

Michael A. Pazos, Waheed Pirzai, Lael M. Yonker, Christophe Morisseau, Karsten Gronert, Bryan P. Hurley

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4)·. We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response.

Original languageEnglish (US)
Pages (from-to)1304-1315
Number of pages12
JournalJournal of Immunology
Volume194
Issue number3
DOIs
StatePublished - Feb 1 2015

Fingerprint

Transendothelial and Transepithelial Migration
Leukotriene B4
Neutrophils
Eicosanoids
Chemotaxis
Chemotactic Factors
Infection
8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid
hepoxilin B4
Cystic Fibrosis
Pseudomonas aeruginosa
Lung Diseases
Pathology
Lung

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration. / Pazos, Michael A.; Pirzai, Waheed; Yonker, Lael M.; Morisseau, Christophe; Gronert, Karsten; Hurley, Bryan P.

In: Journal of Immunology, Vol. 194, No. 3, 01.02.2015, p. 1304-1315.

Research output: Contribution to journalArticle

Pazos, Michael A. ; Pirzai, Waheed ; Yonker, Lael M. ; Morisseau, Christophe ; Gronert, Karsten ; Hurley, Bryan P. / Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration. In: Journal of Immunology. 2015 ; Vol. 194, No. 3. pp. 1304-1315.
@article{5f4e760c0cdc450180581c6123506601,
title = "Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration",
abstract = "Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4)·. We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response.",
author = "Pazos, {Michael A.} and Waheed Pirzai and Yonker, {Lael M.} and Christophe Morisseau and Karsten Gronert and Hurley, {Bryan P.}",
year = "2015",
month = "2",
day = "1",
doi = "10.4049/jimmunol.1402489",
language = "English (US)",
volume = "194",
pages = "1304--1315",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration

AU - Pazos, Michael A.

AU - Pirzai, Waheed

AU - Yonker, Lael M.

AU - Morisseau, Christophe

AU - Gronert, Karsten

AU - Hurley, Bryan P.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4)·. We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response.

AB - Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4)·. We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response.

UR - http://www.scopus.com/inward/record.url?scp=84937633517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937633517&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1402489

DO - 10.4049/jimmunol.1402489

M3 - Article

C2 - 25548217

AN - SCOPUS:84937633517

VL - 194

SP - 1304

EP - 1315

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -