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Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation.
Campbell, Eric L; Bruyninckx, Walter J; Kelly, Caleb J; Glover, Louise E; McNamee, Eóin N; Bowers, Brittelle E; Bayless, Amanda J; Scully, Melanie; Saeedi, Bejan J; Golden-Mason, Lucy; Ehrentraut, Stefan F; Curtis, Valerie F; Burgess, Adrianne; Garvey, John F; Sorensen, Amber; Nemenoff, Raphael; Jedlicka, Paul; Taylor, Cormac T; Kominsky, Douglas J; Colgan, Sean P.
Afiliación
  • Campbell EL; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: eric.campbell@ucdenver.edu.
  • Bruyninckx WJ; Department of Biology, Hanover College, Hanover, IN 47243, USA.
  • Kelly CJ; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Glover LE; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • McNamee EN; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Bowers BE; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Bayless AJ; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Scully M; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Saeedi BJ; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Golden-Mason L; University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Ehrentraut SF; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Curtis VF; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Burgess A; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Garvey JF; University College Dublin, Dublin 4, Ireland.
  • Sorensen A; University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Nemenoff R; University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Jedlicka P; University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Taylor CT; University College Dublin, Dublin 4, Ireland.
  • Kominsky DJ; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Colgan SP; Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Immunity ; 40(1): 66-77, 2014 Jan 16.
Article en En | MEDLINE | ID: mdl-24412613
Acute intestinal inflammation involves early accumulation of neutrophils (PMNs) followed by either resolution or progression to chronic inflammation. Based on recent evidence that mucosal metabolism influences disease outcomes, we hypothesized that transmigrating PMNs influence the transcriptional profile of the surrounding mucosa. Microarray studies revealed a cohort of hypoxia-responsive genes regulated by PMN-epithelial crosstalk. Transmigrating PMNs rapidly depleted microenvironmental O2 sufficiently to stabilize intestinal epithelial cell hypoxia-inducible factor (HIF). By utilizing HIF reporter mice in an acute colitis model, we investigated the relative contribution of PMNs and the respiratory burst to "inflammatory hypoxia" in vivo. CGD mice, lacking a respiratory burst, developed accentuated colitis compared to control, with exaggerated PMN infiltration and diminished inflammatory hypoxia. Finally, pharmacological HIF stabilization within the mucosa protected CGD mice from severe colitis. In conclusion, transcriptional imprinting by infiltrating neutrophils modulates the host response to inflammation, via localized O2 depletion, resulting in microenvironmental hypoxia and effective inflammatory resolution.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colitis / Hipoxia / Membrana Mucosa / Neutrófilos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colitis / Hipoxia / Membrana Mucosa / Neutrófilos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos