Tachykinin substance P signaling involved in diesel exhaust-induced bronchopulmonary neurogenic inflammation in rats.

Abstract

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.

• Authors: Simon S Wong, Nina N Sun, Ingegerd Keith, Chol-Bum Kweon, David E Foster, James J Schauer, Mark L Witten
• Journal: Archives of toxicology (Arch Toxicol) Vol. 77 Issue 11 Pg. 638-50 (Nov 2003) ISSN: 0340-5761 [Print] Germany
• PMID: 13680092 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Radiopharmaceuticals
• Receptors, Neurokinin-1
• Technetium Tc 99m Aggregated Albumin
• Vehicle Emissions
• Substance P
• Endopeptidases
• Capsaicin

Topics

• Animals
• Bronchitis (chemically induced, pathology)
• Capsaicin (toxicity)
• Endopeptidases (metabolism)
• Female
• Immunoenzyme Techniques
• Immunohistochemistry
• Nerve Fibers, Unmyelinated (pathology)
• Neurogenic Inflammation (chemically induced, pathology)
• Neurons, Afferent (pathology)
• Particle Size
• Pneumonia (chemically induced, pathology)
• Radiopharmaceuticals
• Rats
• Rats, Inbred F344
• Receptors, Neurokinin-1 (drug effects)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (physiology)
• Substance P (physiology)
• Technetium Tc 99m Aggregated Albumin
• Vehicle Emissions (toxicity)