The Role of Substance P in Pulmonary Clearance of Bacteria in Comparative Injury Models

Terry Hsieh, Max H. Vaickus, Thor D. Stein, Bethany L. Lussier, Jiyoun Kim, David M. Stepien, Elizabeth R. Duffy, Evan L. Chiswick, Daniel G. Remick

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Neural input to the immune system can alter its ability to clear pathogens effectively. Patients suffering mild traumatic brain injury (mTBI) have shown reduced rates of pneumonia and a murine model replicated these findings, with better overall survival of TBI mice compared with sham-injured mice. To further investigate the mechanism of improved host response in TBI mice, this study developed and characterized a mild tail trauma model of similar severity to mild TBI. Both mild tail trauma and TBI induced similar systemic changes that normalized within 48 hours, including release of substance P. Examination of tissues showed that injuries are limited to the target tissue (ie, tail in tail trauma, brain in mTBI). Pneumonia challenge showed that mild TBI mice showed improved immune responses, characterized by the following: i) increased survival, ii) increased pulmonary neutrophil recruitment, iii) increased bacterial clearance, and iv) increased phagocytic cell killing of bacteria compared with tail trauma. Administration of a neurokinin-1–receptor antagonist to block substance P signaling eliminated the improved survival of mTBI mice. Neurokinin-1–receptor antagonism did not alter pneumonia mortality in tail trauma mice. These data show that immune benefits of trauma are specific to mTBI and that tail trauma is an appropriate control for future studies aimed at elucidating the mechanisms of improved innate immune responses in mTBI mice.

Original languageEnglish (US)
Pages (from-to)3236-3245
Number of pages10
JournalAmerican Journal of Pathology
Volume186
Issue number12
DOIs
StatePublished - Dec 1 2016

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Hsieh, T., Vaickus, M. H., Stein, T. D., Lussier, B. L., Kim, J., Stepien, D. M., Duffy, E. R., Chiswick, E. L., & Remick, D. G. (2016). The Role of Substance P in Pulmonary Clearance of Bacteria in Comparative Injury Models. American Journal of Pathology, 186(12), 3236-3245. https://doi.org/10.1016/j.ajpath.2016.08.014