title: Proliferation of sensory C-fibers and subsequent neurogenic inflammation in rat airway induced by inhaled lipopolysaccharide.
abstract: Lipopolysaccharide (LPS) is associated with the development and exacerbation of airway inflammation. Increases in innervation of sensory C-fibers and tachykinin receptors, which mainly involve overproduction of neurotrophins such as nerve growth factor (NGF), may enhance neurogenic inflammation. Expression of NGF and its receptors in rat lungs is known to decline with age. We examined whether inhaled LPS causes proliferation of sensory C-fibers, increased expression of tachykinin receptors and subsequent enhancement of neurogenic inflammation in the airways of preweaning rats. Wistar male rats aged 2 weeks inhaled aerosolized LPS derived from Escherichia coli (0.1mg/ml) for 30 min. Evans blue dye leakage into the trachea induced by gaseous formaldehyde or intravenous capsaicin was measured as an index of tachykinin NK1 receptor-mediated vascular permeability. Expression of substance P-immunoreactive nerves, tachykinin NK1 receptors, tumor necrosis factor (TNF)-α and NGF in the trachea was also assessed immunohistochemically. Neurogenic plasma leakage in the trachea increased significantly between 7 and 21 days after LPS inhalation. Expression of TNF-α, NGF, substance P-immunoreactive nerves and tachykinin NK1 receptors was enhanced, peaking at 28 h, 7 days, 14 days and 14 days after LPS inhalation, respectively. Pretreatment with infliximab, a blocking antibody for TNF-α, almost completely abolished the airway changes seen after LPS inhalation. In conclusion, inhaled LPS increased innervation of sensory C-fibers and expression of tachykinin NK1 receptors in the airway, probably resulting in enhancement of neurogenic airway inflammation. These airway responses may be caused by overproduction of neurotrophins including NGF, mainly through a TNF-α-mediated pathway.
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Takeda
authors.forename: Mio
authors.initials: M
authors.lastname: Miyake
authors.forename: Taichiro
authors.initials: T
authors.lastname: Muto
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamijima
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Sakamoto
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000367:Age Factors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002199:Capillary Permeability; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D000069285:Infliximab; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020932:Nerve Growth Factor / Q000378:metabolism; D020078:Neurogenic Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013997:Time Factors; D014132:Trachea / Q000098:blood supply / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000336:Aerosols; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D018040:Receptors, Neurokinin-1; D014409:Tumor Necrosis Factor-alpha; C482199:lipopolysaccharide, E coli O55-B5; D013373:Substance P; D020932:Nerve Growth Factor; D000069285:Infliximab