Weinstock Joel V
James A Clifton Center for Digestive Diseases, Department of Internal Medicine, University of Iowa Roy J and Lucille Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Front Biosci. 2004 May 1;9:1936-43. doi: 10.2741/1375.
Granulomas are chronic inflammations that prevent spread of poorly controllable infectious agents. The gut lumen contains enteric organisms that are excluded from the host by leukocytes located in the intestinal lining. Physiological intestinal inflammation and granulomas share some similarities. Both function to confine, but not necessarily abolish potentially harmful factors. Also, both are subject to intense immune regulation to avoid unnecessary tissue injury. Substance P and its natural analog hemokinin are produced at these sites of inflammation and are important components of this regulatory process. They act through a shared receptor (NK-1) expressed on T cells, macrophages, dendritic cells and probably other cell types. One of their functions is to enhance IFN-gamma production and amplify the Th1 response. The NK-1 receptor is an important target for immune regulation. Several Th1 cytokines and T cell antigen receptor (TCR) activation induce NK-1 receptor expression on T cells, while IL-10 and TGF-beta block receptor display. Macrophages also have an inducible NK-1 receptor. Various types of immune cells can make substance P and hemokinin, whose syntheses also are subject to immunoregulation. Thus, substance P and hemokinin are inflammatory cytokines with overlapping functions that help control immune responses in granulomas and at mucosal surfaces, and probably elsewhere.
肉芽肿是一种慢性炎症，可防止难以控制的传染源扩散。肠腔内含有肠道微生物，位于肠壁的白细胞可将这些微生物排除在宿主体外。生理性肠道炎症和肉芽肿有一些相似之处。两者都起到限制作用，但不一定能消除潜在的有害因素。此外，两者都受到严格的免疫调节，以避免不必要的组织损伤。P物质及其天然类似物血激肽在这些炎症部位产生，是这一调节过程的重要组成部分。它们通过T细胞、巨噬细胞、树突状细胞以及可能其他细胞类型上表达的共同受体（NK-1）发挥作用。它们的功能之一是增强γ干扰素的产生并放大Th1反应。NK-1受体是免疫调节的重要靶点。几种Th1细胞因子和T细胞抗原受体（TCR）激活可诱导T细胞上NK-1受体的表达，而白细胞介素-10和转化生长因子-β则会阻断受体的表达。巨噬细胞也有可诱导的NK-1受体。各种类型的免疫细胞都能产生P物质和血激肽，它们的合成也受到免疫调节。因此，P物质和血激肽是具有重叠功能的炎性细胞因子，有助于控制肉芽肿和黏膜表面以及可能其他部位的免疫反应。
