SUBSTANCE P-IMMUNOREACTIVE SENSORY AXONS IN THE RAT RESPIRATORY-TRACT - A QUANTITATIVE STUDY OF THEIR DISTRIBUTION AND ROLE IN NEUROGENIC INFLAMMATION
SUBSTANCE P-IMMUNOREACTIVE SENSORY AXONS IN THE RAT RESPIRATORY-TRACT - A QUANTITATIVE STUDY OF THEIR DISTRIBUTION AND ROLE IN NEUROGENIC INFLAMMATION
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DOI：
10.1002/cne.903190408
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发表时间：
1992-05-22
影响因子：
2.5
通讯作者：
MCDONALD, DM
中科院分区：
文献类型：
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作者：
BALUK, P;NADEL, JA;MCDONALD, DM
P物质是感觉神经释放的一种肽，可介导“神经源性炎症”。“虽然已知P物质免疫反应（SP-IR）轴突存在于呼吸道粘膜内，但粘膜各种成分的神经支配的相对程度尚不清楚。因此，我们用免疫组织化学的方法测定了大鼠气管和支气管中SP-IR轴突的分布和数量。具体来说，我们试图了解这些轴突是否直接支配毛细血管后小静脉参与神经源性血浆外渗，参与神经源性血管舒张的小动脉，和气道平滑肌参与支气管收缩在无病原体，成年雄性F344大鼠。我们发现90%的SP-IR轴突是单轴突，通常具有静脉曲张。其中85%在上皮细胞中，6%在受神经支配的小动脉中，其余在固有层中的其他地方。只有10%的介质敏感的毛细血管后微静脉（即，在用辣椒素或P物质刺激后用单星蓝色素标记的微静脉在SP-IR轴突的10 μ m内。SP-IR轴突在远端支气管平滑肌中的频率是在气管中的10倍以上。辣椒素预处理（168 mg/kg，7天）使气管中SP-IR轴突的数量减少了96%，这与它们的感觉一致。单侧迷走神经切断术减少了双侧气管和同侧主支气管中SP-IR轴突的数量。使用蛋白质基因产物9.5的抗体作为气管中所有神经的非特异性标记物，我们确定SP-IR轴突构成上皮中轴突的90%，小动脉中轴突的32%，平滑肌中轴突的仅4%。我们的结论是，大多数SP-IR神经在气管感觉轴突和这些轴突的大多数结束在上皮。SP-IR轴突支配粘膜小动脉，但很少支配毛细血管后微静脉。因此，感觉轴突引起血浆从这些小静脉外渗的机制可能涉及肽或次级介质从上皮或从小动脉上游的扩散。
Substance P is one of the peptides released from sensory nerves that mediate "neurogenic inflammation." Although substance P-immunoreactive (SP-IR) axons are known to be present within the mucosa of the respiratory tract, the relative extent of the innervation of various components of the mucosa is not known. Therefore, we determined the distribution and number of SP-IR axons in the rat trachea and bronchi, by using immunohistochemistry on tissue whole mounts. Specifically, we sought to learn whether these axons directly innervate the postcapillary venules involved in neurogenic plasma extravasation, the arterioles involved in neurogenic vasodilatation, and the airway smooth muscle involved in bronchoconstriction in pathogen-free, adult male F344 rats. We found that 90% of the SP-IR axons were single axons, usually having varicosities. Eighty-five percent of these were in the epithelium, 6% innervated arterioles, and the remainder elsewhere in the lamina propria. Only 10% of the mediator-sensitive postcapillary venules (i.e., venules labeled with Monastral blue pigment after challenge with capsaicin or substance P) were within 10-mu-m of SP-IR axons. SP-IR axons were more than 10 times as frequent in the smooth muscle of the distal bronchi as in the trachea. Capsaicin pretreatment (168 mg/kg over 7 days) reduced the number of SP-IR axons in the trachea by 96%, which is consistent with their being sensory. Unilateral vagotomy reduced the number of SP-IR axons bilaterally in the trachea and ipsilaterally in the main stem bronchus. Using an antibody to Protein Gene Product 9.5 as a nonspecific marker for all nerves in the trachea, we determined that SP-IR axons constituted 90% of the axons in the epithelium, 32% of the axons on arterioles, and only 4% of the axons in the smooth muscle. We conclude that most SP-IR nerves in the trachea are sensory axons and most of these axons end in the epithelium. SP-IR axons innervate mucosal arterioles, but few innervate postcapillary venules. Therefore, the mechanism by which sensory axons evoke plasma extravasation from these venules is likely to involve the diffusion of the peptide or a secondary mediator from the epithelium or from the arterioles upstream.