Appleton I, Tomlinson A, Colville-Nash P R, Willoughby D A
Department of Experimental Pathology, William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, United Kingdom.
Lab Invest. 1993 Oct;69(4):405-14.
Cytokines have profound effects on various aspects of granulomatous tissue formation. However, there is little information regarding their distribution during tissue development. This study investigated the temporal and spatial distribution of transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1) and IL-1 beta in developing granulomatous tissue.
Murine chronic granulomatous air pouches were induced and full thickness biopsies taken at intervals up to 28 days. Samples were prepared for immunohistochemistry and labeled using antibodies against TGF-beta, bFGF, PDGF, EGF, TNF-alpha, IL-1 alpha and IL-1 beta.
Immunoreactivity to TGF-beta, PDGF, TNF-alpha, IL-1 alpha and IL-1 beta was localized to a proportion of macrophages within the granulomatous tissue. Immunopositive macrophage numbers increased with time, and with the exception of PDGF were associated with areas of fibrogenesis between days 14 to 28. Heterogeneous labeling of capillaries for EGF was observed within the granulomatous tissue juxtaposed to dermal musculature. Diffuse labeling of bFGF, associated with extracellular matrix, was always observed. After day 14, bFGF immunoreactivity was discretely localized to endothelial cells and the basement membrane of vessels within the granulomatous tissue. TGF-beta immunoreactivity was also associated with extracellular matrix components, being most intense in the area of fibrogenesis between 14 and 28 days. Occasional fibroblasts were also labeled with TGF-beta in this region.
The spatial and temporal confinement of the individual cytokines suggests that a sequential coordinated process of repair and fibrosis is occurring. It is hoped that these observations will provide a more effective therapeutic approach for the sequential application of cytokines in abnormalities of wound healing.
细胞因子对肉芽肿组织形成的各个方面具有深远影响。然而，关于它们在组织发育过程中的分布情况，相关信息甚少。本研究调查了转化生长因子-β（TGF-β）、血小板衍生生长因子（PDGF）、表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1α（IL-1）和IL-1β在发育中的肉芽肿组织中的时空分布。
诱导小鼠慢性肉芽肿气袋形成，并在长达28天的时间间隔内取全层活检组织。样本经制备用于免疫组织化学，并使用抗TGF-β、bFGF、PDGF、EGF、TNF-α、IL-1α和IL-1β的抗体进行标记。
对TGF-β、PDGF、TNF-α、IL-1α和IL-1β的免疫反应性定位于肉芽肿组织内的一部分巨噬细胞。免疫阳性巨噬细胞数量随时间增加，除PDGF外，在第14至28天与纤维生成区域相关。在与真皮肌肉组织相邻的肉芽肿组织内观察到毛细血管对EGF的异质性标记。总是观察到与细胞外基质相关的bFGF弥漫性标记。第14天后，bFGF免疫反应性离散地定位于肉芽肿组织内血管的内皮细胞和基底膜。TGF-β免疫反应性也与细胞外基质成分相关，在第14至28天的纤维生成区域最为强烈。在该区域偶尔也有一些成纤维细胞被TGF-β标记。
单个细胞因子的时空局限性表明正在发生一个连续协调的修复和纤维化过程。希望这些观察结果将为在伤口愈合异常中顺序应用细胞因子提供一种更有效的治疗方法。
