Oslund Karen L, Hyde Dallas M, Putney Leialoha F, Alfaro Mario F, Walby William F, Tyler Nancy K, Schelegle Edward S
The Center for Comparative Respiratory Biology and Medicine, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Toxicol Pathol. 2009 Oct;37(6):805-13. doi: 10.1177/0192623309345691. Epub 2009 Aug 21.
The authors investigated the importance of the neuropeptide, calcitonin gene-related peptide (CGRP), in epithelial injury, repair, and neutrophil emigration after ozone exposure. Wistar rats were administered either a CGRP-receptor antagonist (CGRP(8-37)) or saline and exposed to 8 hours of 1-ppm ozone or filtered air with an 8-hour postexposure period. Immediately after exposure, ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, airway dissected lung lobes were stained for 5'-bromo-2'-deoxyuridine, a marker of epithelial proliferation. Positive epithelial cells were quantified in specific airway generations. Rats treated with CGRP(8-37) had significantly reduced epithelial injury in terminal bronchioles and reduced epithelial proliferation in proximal airways and terminal bronchioles. Bronchoalveolar lavage and sections of terminal bronchioles showed no significant difference in the number of neutrophils emigrating into airways in CGRP(8-37)-treated rats. The airway epithelial cell line, HBE-1, showed no difference in the number of oxidant stress positive cells during exposure to hydrogen peroxide and a range of CGRP(8-37) doses, demonstrating no antioxidant effect of CGRP(8-37). We conclude that activation of CGRP receptors during ozone inhalation contributes to airway epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.
作者研究了神经肽降钙素基因相关肽（CGRP）在臭氧暴露后上皮损伤、修复及中性粒细胞迁移中的重要性。给Wistar大鼠注射CGRP受体拮抗剂（CGRP(8 - 37)）或生理盐水，然后让其暴露于1 ppm的臭氧中8小时或过滤空气中8小时，并在暴露后有8小时的恢复期。暴露后立即将乙锭同二聚体注入肺中，作为坏死气道上皮细胞的标志物。固定后，对解剖的肺叶气道进行5'-溴-2'-脱氧尿苷染色，这是上皮增殖的标志物。对特定气道代中的阳性上皮细胞进行定量。用CGRP(8 - 37)处理的大鼠终末细支气管上皮损伤明显减轻，近端气道和终末细支气管上皮增殖减少。支气管肺泡灌洗和终末细支气管切片显示，用CGRP(8 - 37)处理的大鼠气道中迁移的中性粒细胞数量无显著差异。气道上皮细胞系HBE - 1在暴露于过氧化氢和一系列CGRP(8 - 37)剂量期间，氧化应激阳性细胞数量无差异，表明CGRP(8 - 37)无抗氧化作用。我们得出结论，臭氧吸入期间CGRP受体的激活导致气道上皮损伤及随后的上皮增殖，这是修复的关键组成部分，但不影响中性粒细胞向气道的迁移。
