You are here: Home Published Research Cigarette smoke primes the pulmonary environment to IL-1α/CXCR-2-dependent nontypeable Haemophilus influenzae-exacerbated neutrophilia in mice.

Jake K Nikota, Pamela Shen, Mathieu C Morissette, Kimberly Fernandes, Abraham Roos, Derek K Chu, Nicole G Barra, Yoichiro Iwakura, Roland Kolbeck, Alison A Humbles, and Martin R Stampfli (2014)

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

Journal of immunology (Baltimore, Md. : 1950), 193(6):3134–3145.

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.

Animals, Bronchoalveolar Lavage Fluid, Cells, Cultured, Chemokine CXCL1, Chemokine CXCL5, Female, Haemophilus Infections, Haemophilus influenzae, Inflammation, Interleukin-1alpha, Leukocyte Count, Lung, Macrophages, Alveolar, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Neutrophil Infiltration, Neutrophils, Pulmonary Disease, Chronic Obstructive, RNA, Messenger, Receptors, Interleukin-8B, Respiratory Mucosa, Smoke, Tobacco
Animals, Bronchoalveolar Lavage Fluid, Cells, Cultured, Chemokine CXCL1, Chemokine CXCL5, Female, Haemophilus Infections, Haemophilus influenzae, Inflammation, Interleukin-1alpha, Leukocyte Count, Lung, Macrophages, Alveolar, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Neutrophil Infiltration, Neutrophils, Pulmonary Disease, Chronic Obstructive, RNA, Messenger, Receptors, Interleukin-8B, Respiratory Mucosa, Smoke, Tobacco
 
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