Tachykinin substance P signaling involved in diesel exhaust-induced bronchopulmonary neurogenic inflammation in rats.
This study characterizes the molecular neurotoxicity of diesel exhaust (DE) on the tachykinin substance P (SP) signaling system in the lungs. A total of 96 female Fischer 344/NH rats (approximately 175 g, approximately 4 weeks old) were randomly assigned to eight groups in a 2 x4 factorial design: capsaicin versus non-capsaicin (vehicle) pretreatment, and filtered room air versus two exposure levels of DE with diesel engine room control. The rats were exposed nose-only to room air or low (35.3 micro g/m(3)) and high concentrations (669.3 micro g/m(3)) particulates directly from a Cummins N14 research engine at 75% throttle for 4 h/day, 5 days/week, for 3 weeks. The findings showed that exposure to DE dose-dependently induced bronchopulmonary neurogenic inflammation, both in capsaicin- and vehicle-pretreated rats, as measured by plasma extravasation, edema, and inflammatory cells. DE inhalation affected the SP signaling processes, including stored SP depletion and the gene/protein overexpression for neurokinin-1 receptor. DE also significantly reduced the activity of neutral endopeptidase, a main degradation enzyme for SP. Consequently, these changes may be regarded as critical factors that switched neurogenic pulmonary responses from their protective functions to a detrimental role that perpetuates lung inflammation. These changes may possibly be associated with the mass concentration of DE particles due to their physico-chemical characteristics. Moreover, capsaicin-pretreated rats had more sensitivity to these levels of DE exposure due to stimulation of bronchopulmonary C-fibers. However, the effects of capsaicin treatment were not consistent and apparent in this study. Taken together, our findings suggest that neurokininergic mechanisms may possibly be involved in DE-induced lung inflammation, but that bronchopulmonary C-fibers did not dominate DE-induced inflammatory abnormalities.
D000818:Animals; D001991:Bronchitis / Q000139:chemically induced* / Q000473:pathology*; D002211:Capsaicin / Q000633:toxicity; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D020078:Neurogenic Inflammation / Q000139:chemically induced* / Q000473:pathology*; D009475:Neurons, Afferent / Q000473:pathology; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology*; D019275:Radiopharmaceuticals; D051381:Rats; D011916:Rats, Inbred F344; D018040:Receptors, Neurokinin-1 / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013373:Substance P / Q000502:physiology*; D013668:Technetium Tc 99m Aggregated Albumin; D001335:Vehicle Emissions / Q000633:toxicity*
D019275:Radiopharmaceuticals; D018040:Receptors, Neurokinin-1; D013668:Technetium Tc 99m Aggregated Albumin; D001335:Vehicle Emissions; D013373:Substance P; D010450:Endopeptidases; D002211:Capsaicin