Stead R H, Tomioka M, Quinonez G, Simon G T, Felten S Y, Bienenstock J
Proc Natl Acad Sci U S A. 1987 May;84(9):2975-9. doi: 10.1073/pnas.84.9.2975.
Inflammatory or allergic conditions, as well as situations where healing and repair processes occur, are characterized by the presence of increased numbers of mast cells. Previous work on the effect of neuropeptides on mast cell mediator release showed that only substance P caused such release from intestinal mucosal mast cells [Shanahan, F., Denburg, J. A., Fox, J., Bienenstock, J. & Befus, A. D. (1985) J. Immunol. 135, 1331-1337]. Accordingly, we investigated the microanatomical relationship between mast cells and enteric nerves in normal rat intestine and parasite-infected rat intestine, in which mucosal mast cell hyperplasia occurs. Combined immunohistochemistry for neuron-specific enolase and staining with alcian blue at pH 0.5 was employed on paraffin-embedded sections of normal and Nippostrongylus brasiliensis-infected rat jejunum. Sixty-seven percent of intestinal mucosal mast cells were touching subepithelial nerves, and an additional 20% were within 2 micron of nerves. Assessment of the proportion of the lamina propria occupied by mast cells (12.5%), the average mast cell area (121 +/- 28 microns 2), and the density of enteric nerves (one per 788 +/- 151 microns 2) suggested that the association was 5 times greater than would be expected by chance alone (P less than 0.0001). In consecutive sections, the nerves in contact with mast cells were also shown to contain substance P and/or calcitonin-gene-related peptide. Electron microscopy confirmed this association: 8% of the mast cells in infected rats exhibited membrane-membrane contact with unmyelinated axons containing 70- to 170-nm dense-core vesicles, and an additional 31% were situated less than 250 nm from nerves. Other mast cells appeared to embrace nerve bundles through the projection of lamellopodia. These data provide systematic quantitative evidence that a structural foundation for communication between the immune and nervous systems exists in the rat gastrointestinal tract.
炎症或过敏状态，以及愈合和修复过程发生的情况，其特征是肥大细胞数量增加。先前关于神经肽对肥大细胞介质释放影响的研究表明，只有P物质能引起肠黏膜肥大细胞释放介质[沙纳汉，F.，登伯格，J. A.，福克斯，J.，比嫩斯托克，J. & 贝富斯，A. D.（1985年）《免疫学杂志》135卷，1331 - 1337页]。因此，我们研究了正常大鼠肠道和寄生虫感染大鼠肠道（其中发生黏膜肥大细胞增生）中肥大细胞与肠神经之间的微观解剖关系。对正常和巴西日圆线虫感染的大鼠空肠石蜡包埋切片进行神经元特异性烯醇化酶的联合免疫组织化学和pH 0.5的阿尔辛蓝染色。67%的肠黏膜肥大细胞与上皮下神经接触，另外20%位于神经的2微米范围内。对固有层中肥大细胞所占比例（12.5%）、肥大细胞平均面积（121±28平方微米）和肠神经密度（每788±151平方微米有一条）的评估表明，这种关联比仅由偶然因素预期的大5倍（P小于0.0001）。在连续切片中，与肥大细胞接触的神经也显示含有P物质和/或降钙素基因相关肽。电子显微镜证实了这种关联：感染大鼠中8%的肥大细胞与含有70至170纳米致密核心小泡的无髓轴突存在膜 - 膜接触，另外31%位于距离神经不到250纳米处。其他肥大细胞似乎通过片状伪足的突起包裹神经束。这些数据提供了系统的定量证据，表明大鼠胃肠道中存在免疫和神经系统之间通信的结构基础。
