Bowden J J, Baluk P, Lefevre P M, Schoeb T R, Lindsey J R, McDonald D M
Cardiovascular Research Institute, University of California, San Francisco 94143, USA.
Am J Physiol. 1996 Mar;270(3 Pt 1):L393-403. doi: 10.1152/ajplung.1996.270.3.L393.
Mycoplasma pulmonis infection in rats results in life-long disease, characterized by chronic inflammation of the airway mucosa with widespread accumulation of lymphoid tissue, mucous cell hyperplasia, and mucosal thickening. In addition, there is angiogenesis and increased sensitivity of mucosal blood vessels to substance P (SP), so tachykinins released from sensory nerve fibers cause an abnormally large amount of plasma leakage. We sought to learn whether the sensory nerves influence the severity of the chronic inflammatory response of M. pulmonis infection. Our strategy was to destroy the nerves by capsaicin pretreatment at birth, infect the rats with M. pulmonis at 8 wk of age, and then study the animals 6 wk later. We found that capsaicin pretreatment increased the severity of the infection, exaggerated the pathological changes in the tracheal mucosa, and increased the amount of SP-induced plasma leakage, as quantified with Monastral blue. The thickness of the tracheal mucosa in these infected rats was 80% greater than in their vehicle-pretreated counterparts and 200% greater than in the pathogen-free controls. The area density of Monastral blue-labeled blood vessels averaged 20% in the infected rats pretreated with capsaicin, which represented a 40-fold increase over the leakage in the pathogen-free group. By comparison, the amount of Monastral blue labeling was only 13% in rats pretreated with vehicle (P<0.05), which was a 22-fold increase over the corresponding pathogen-free group. The number of SP-immunoreactive nerve fibers was reduced both by neonatal capsaicin and by infection (87 and 63% reductions, respectively); but when the two conditions were combined, their effects were not additive (79% reduction), perhaps because of nerve regrowth. We conclude that destruction of sensory nerves increases the severity of infection- induced chronic inflammation in the airway mucosa, with exaggerated mucosal thickening, angiogenesis, plasma leakage, and nerve remodeling.
大鼠肺部支原体感染会导致终身疾病，其特征为气道黏膜慢性炎症，伴有淋巴组织广泛积聚、黏液细胞增生和黏膜增厚。此外，还存在血管生成以及黏膜血管对P物质（SP）的敏感性增加，因此感觉神经纤维释放的速激肽会导致异常大量的血浆渗漏。我们试图了解感觉神经是否会影响肺部支原体感染慢性炎症反应的严重程度。我们的策略是在出生时用辣椒素预处理破坏神经，在8周龄时用肺部支原体感染大鼠，然后在6周后研究这些动物。我们发现，辣椒素预处理会增加感染的严重程度，加剧气管黏膜的病理变化，并增加SP诱导的血浆渗漏量，用天青蓝进行定量分析。这些感染大鼠的气管黏膜厚度比用赋形剂预处理的对应大鼠厚80%，比无病原体对照组厚200%。在用辣椒素预处理的感染大鼠中，天青蓝标记血管的面积密度平均为20%，这比无病原体组的渗漏量增加了40倍。相比之下，用赋形剂预处理的大鼠中天青蓝标记量仅为13%（P<0.05），这比相应的无病原体组增加了22倍。新生期辣椒素处理和感染都会减少SP免疫反应性神经纤维的数量（分别减少87%和63%）；但当这两种情况同时存在时，它们的作用并非相加性的（减少79%），这可能是由于神经再生。我们得出结论，感觉神经破坏会增加气道黏膜感染诱导的慢性炎症的严重程度，伴有加剧的黏膜增厚、血管生成、血浆渗漏和神经重塑。
