Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation

Mara Chavolla-Calderón, Meggan K. Bayer, J. Julio Pérez Fontán

Research output: Contribution to journalArticle

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Abstract

Neurogenic inflammation is believed to originate with the antidromic release of substance P, and of other neurokinins encoded by the preprotachykinin A (PPT-A) gene, from unmyelinated nerve fibers (C-fibers) following noxious stimuli. Consistent with this concept, we show here that selective sensory-fiber denervation with capsaicin and targeted deletion of the PPT-A gene protect murine lungs against both immune complex-mediated and stretch-mediated injuries. Reconstitution of PPT-A gene-deleted mice with WT bone marrow does not abrogate this protection, demonstrating a critical role for PPT-A gene expression by sensory neurons in pulmonary inflammation. Surprisingly, reconstitution of WT mice with PPT-A gene-deficient bone marrow also confers protection against pulmonary injury, revealing that PPT-A gene expression in hemopoietic cells has a previously unanticipated essential role in tissue injury. Taken together, these findings demonstrate a critical synergy between capsaicin-sensitive sensory fibers and hemopoietic cells in neurokinin-mediated inflammation and suggest that such synergy may be the basis for a stereotypical mechanism of response to injury in the respiratory tract.

Original languageEnglish (US)
Pages (from-to)973-980
Number of pages8
JournalJournal of Clinical Investigation
Volume111
Issue number7
DOIs
Publication statusPublished - Apr 2003

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ASJC Scopus subject areas

  • Medicine(all)

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