Walters Dianne M, Breysse Patrick N, Schofield Brian, Wills-Karp Marsha
Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, USA.
Am J Respir Cell Mol Biol. 2002 Oct;27(4):413-8. doi: 10.1165/rcmb.4844.
Epidemiologic studies have suggested that exposure to airborne particulate matter (PM) can exacerbate allergic airway responses; however, the mechanism(s) are not well understood. We and others have recently shown that development of airway hyperresponsiveness (AHR) may be a complement-mediated process. In the present study, we examined the role of complement factor 3 (C3) in the development of PM-induced AHR and airway inflammation by comparing responses between C3-deficient (C3(-/-)) and wild-type mice. Mice were exposed to 0.5 mg of ambient particulate collected in urban Baltimore. Forty-eight hours later, airway responsiveness to intravenous acetylcholine was assessed and bronchoalveolar lavage was conducted. PM exposure of wild-type mice resulted in significant increases in AHR, whereas it did not significantly increase airway reactivity in C3(-/-) mice. Interestingly, PM induced similar inflammatory responses in both wild-type and C3(-/-) mice. Immunohistochemical staining demonstrated marked C3 deposition in the airway epithelium and connective tissue of wild-type mice after PM exposure. These results suggest that exposure to PM may induce AHR through activation of complement factor 3 in the airways.
流行病学研究表明，接触空气中的颗粒物（PM）会加剧过敏性气道反应；然而，其机制尚未完全明确。我们和其他研究人员最近发现，气道高反应性（AHR）的发生可能是一个补体介导的过程。在本研究中，我们通过比较C3缺陷（C3(-/-)）小鼠和野生型小鼠的反应，研究了补体因子3（C3）在PM诱导的AHR和气道炎症发展中的作用。将小鼠暴露于在巴尔的摩市收集的0.5毫克环境颗粒物中。48小时后，评估气道对静脉注射乙酰胆碱的反应性，并进行支气管肺泡灌洗。野生型小鼠暴露于PM后，AHR显著增加，而C3(-/-)小鼠的气道反应性未显著增加。有趣的是，PM在野生型和C3(-/-)小鼠中诱导了相似的炎症反应。免疫组织化学染色显示，PM暴露后野生型小鼠的气道上皮和结缔组织中有明显的C3沉积。这些结果表明，接触PM可能通过激活气道中的补体因子3诱导AHR。
