title: Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation.
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.
authors.affiliation: The Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Mara
authors.initials: M
authors.lastname: Chavolla-Calderón
authors.forename: Meggan K
authors.initials: MK
authors.lastname: Bayer
authors.forename: J Julio Pérez
authors.initials: JJ
authors.lastname: Fontán
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002211:Capsaicin / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007107:Immune System; D007249:Inflammation; D008024:Ligands; D008168:Lung / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D015288:Neurokinin A / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology; D012119:Respiration; D013373:Substance P / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014132:Trachea / Q000378:metabolism
chemical_list: D008024:Ligands; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D015288:Neurokinin A; D002211:Capsaicin