Abstract
Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and reduces pulmonary bacterial infection after inhalation injury
The Journal of immunology (1950), Vol.200(1_Supplement), pp.114-114.23
05/01/2018
DOI: 10.4049/jimmunol.200.Supp.114.23
Abstract
Smoke inhalation associated with structural fires, wildfires, or explosions leads to lung injury. Clinically relevant animal models are needed to develop therapeutics. We have previously reported that damage associated molecular patterns (DAMPs) and anti-inflammatory cytokines correlate with infectious complications in patients diagnosed with inhalational injury. We describe a novel translational murine model of acute inhalational injury characterized by an accumulation of protein and neutrophils in the bronchoalveolar space, and histological evidence of tissue damage. Mice were anesthetized, a cannula placed in the trachea, and exposed to smoldering plywood smoke three times for two minute intervals. Here we demonstrate that this model recapitulates clinically relevant phenotypes including early release of dsDNA, IL-10, MCP-1, and CXCL1 along with neutrophilia early after injury, accompanied by subsequent susceptibility to opportunistic infection with Pseudomonas aeruginosa. The mouse model, and a re-analysis of patient samples, revealed a late release of the DAMP hyaluronic acid (HA) from the lung. Using nitric oxide synthase deficient (Nos2−/−) mice, we found that Nos2 was required for increases in IL-10, MCP-1, and HA following injury but not release of dsDNA, CXCL1 expression, early neutrophilia, nor susceptibility to opportunistic infection. Depletion of CXCL1 attenuated early neutrophil recruitment, leading to decreased histopathology scores and improved bacterial clearance in this model of smoke inhalation compared to untreated injured mice. These data highlight the potential therapeutic benefit of attenuating neutrophil recruitment in the first 24h after injury in patients.
Details
- Title: Subtitle
- Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and reduces pulmonary bacterial infection after inhalation injury
- Creators
- Robert Maile - University of North Carolina at Chapel HillJulia L. Dunn - University of North Carolina at Chapel HillLaurel B. Kartchner - University of North Carolina at Chapel HillSamuel W. Jones - University of North Carolina at Chapel HillBruce A. Cairns - University of North Carolina at Chapel Hill
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.200(1_Supplement), pp.114-114.23
- DOI
- 10.4049/jimmunol.200.Supp.114.23
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2018
- Academic Unit
- Surgery
- Record Identifier
- 9984757275502771
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