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J Immunol. 2014 Sep 15;193(6):3134-45. doi: 10.4049/jimmunol.1302412. Epub 2014 Aug 4.

Cigarette smoke primes the pulmonary environment to IL-1α/CXCR-2-dependent nontypeable Haemophilus influenzae-exacerbated neutrophilia in mice.

Author information

  • 1Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario L8S 4K1, Canada;
  • 2Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8S 4K1, Canada;
  • 3Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo 113-8654, Japan;
  • 4MedImmune LLC, Gaithersburg, MD 20878; and.
  • 5Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8S 4K1, Canada; Department of Medicine, Firestone Institute for Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, Ontario L8N 4A6, Canada.

Abstract

Cigarette smoke has a broad impact on the mucosal environment with the ability to alter host defense mechanisms. Within the context of a bacterial infection, this altered host response is often accompanied by exacerbated cellular inflammation, characterized by increased neutrophilia. The current study investigated the mechanisms of neutrophil recruitment in a murine model of cigarette smoke exposure and, subsequently, a model of both cigarette smoke exposure and bacterial infection. We investigated the role of IL-1 signaling in neutrophil recruitment and found that cigarette smoke-induced neutrophilia was dependent on IL-1α produced by alveolar macrophages. In addition to being the crucial source of IL-1α, alveolar macrophages isolated from smoke-exposed mice were primed for excessive IL-1α production in response to bacterial ligands. To test the relevance of exaggerated IL-1α production in neutrophil recruitment, a model of cigarette smoke exposure and nontypeable Haemophilus influenzae infection was developed. Mice exposed to cigarette smoke elaborated an exacerbated CXCR2-dependent neutrophilia in response to nontypeable Haemophilus influenzae. Exacerbated neutrophilia was dependent on IL-1α priming of the pulmonary environment by cigarette smoke as exaggerated neutrophilia was dependent on IL-1 signaling. These data characterize a novel mechanism of cigarette smoke priming the lung mucosa toward greater IL-1-driven neutrophilic responses to bacteria, with a central role for the alveolar macrophage in this process.

Copyright © 2014 by The American Association of Immunologists, Inc.

PMID:
25092891
[PubMed - indexed for MEDLINE]
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