Meek R M, McLellan S, Crossan J F
University Department of Orthopaedics, Western Infirmary, Glasgow, Scotland, UK.
J Bone Joint Surg Br. 1999 Jul;81(4):732-8. doi: 10.1302/0301-620x.81b4.9163.
Dupuytren's disease is a chronic inflammatory process which produces contractures of the fingers. The nodules present in Dupuytren's tissue contain inflammatory cells, mainly lymphocytes and macrophages. These express a common integrin known as VLA4. The corresponding binding ligands to VLA4 are vascular cell adhesion molecule-1 (VCAM-1) present on the endothelial cells and the CS1 sequence of the fibronectin present in the extracellular matrix. Transforming growth factor-beta (TGF-beta) is a peptide hormone which has a crucial role in the process of fibrosis. We studied tissue from 20 patients with Dupuytren's disease, four samples of normal palmar fascia from patients undergoing carpal tunnel decompression and tissue from ten patients who had received perinodular injections of depomedrone into the palm five days before operation. The distribution of VLA4, VCAM-1, CS1 fibronectin and TGF-beta was shown by immunohistochemistry using an alkaline phosphorylase method for light microscopy. In untreated Dupuytren's tissue CS1 fibronectin stained positively around the endothelial cells of blood vessels and also around the surrounding myofibroblasts, principally at the periphery of many of the active areas of the Dupuytren's nodule. VCAM-1 stained very positively for the endothelial cells of blood vessels surrounding and penetrating the areas of high nodular activity. VCAM-1 was more rarely expressed outside the blood vessels. VLA4 was expressed by inflammatory cells principally in and around the blood vessels expressing VCAM-1 and CS1 but also on some cells spreading into the nodule. TGF-beta stained positively around the inflammatory cells principally at the perivascular periphery of nodules. These cells often showed VLA4 expression and co-localised with areas of strong production of CS1 fibronectin. Normal palmar fascia contained only scanty amounts of CS1 fibronectin, almost no VCAM-1 and only an occasional cell staining positively for VLA4 or TGF-beta. In the steroid-treated group, VCAM-1 expression was downregulated in the endothelium of perinodular blood vessels and only occasional inflammatory cell expression remained. Expression of CS1 fibronectin was also much reduced but still occurred in the blood vessels and around the myofibroblast stroma. VLA4-expressing cells were also reduced in numbers. A similar but reduced distribution of production of TGF-beta was also noted. Our findings show that adherence of inflammatory cells to the endothelial wall and the extravasation into the periphery of the nodule may be affected by steroids, which reduce expression of VCAM-1 in vivo. This indicates that therapeutic intervention to prevent the recommencement of the chronic inflammatory process and subsequent fibrosis necessitating further surgery may be possible.
掌腱膜挛缩症是一种导致手指挛缩的慢性炎症过程。掌腱膜挛缩症组织中的结节含有炎症细胞，主要是淋巴细胞和巨噬细胞。这些细胞表达一种名为VLA4的常见整合素。VLA4的相应结合配体是内皮细胞上存在的血管细胞黏附分子-1（VCAM-1）以及细胞外基质中纤连蛋白的CS1序列。转化生长因子-β（TGF-β）是一种肽类激素，在纤维化过程中起关键作用。我们研究了20例掌腱膜挛缩症患者的组织、4例接受腕管减压手术患者的正常掌腱膜样本以及10例术前五天在手掌结节周围注射曲安奈德的患者的组织。采用碱性磷酸酶法进行免疫组织化学染色，通过光学显微镜观察VLA4、VCAM-1、CS1纤连蛋白和TGF-β的分布。在未经治疗的掌腱膜挛缩症组织中，CS1纤连蛋白在血管内皮细胞周围以及周围的肌成纤维细胞周围呈阳性染色，主要在掌腱膜挛缩症结节许多活跃区域的周边。VCAM-1在围绕并穿透高结节活性区域的血管内皮细胞上染色非常阳性。VCAM- 在血管外很少表达。VLA4主要由炎症细胞在表达VCAM-1和CS1的血管内及周围表达，但也在一些蔓延到结节内的细胞上表达。TGF-β在炎症细胞周围呈阳性染色，主要在结节的血管周围周边。这些细胞通常显示VLA4表达，并与CS1纤连蛋白大量产生的区域共定位。正常掌腱膜仅含有少量CS1纤连蛋白，几乎没有VCAM-1，只有偶尔的细胞对VLA4或TGF-β呈阳性染色。在类固醇治疗组中，结节周围血管内皮细胞中的VCAM-1表达下调，仅残留偶尔的炎症细胞表达。CS1纤连蛋白的表达也大幅降低，但仍在血管和肌成纤维细胞基质周围出现。表达VLA4的细胞数量也减少。还注意到TGF-β产生的分布类似但减少。我们的研究结果表明，炎症细胞与内皮壁的黏附以及向结节周边的渗出可能受到类固醇的影响，类固醇在体内会降低VCAM-1的表达。这表明有可能进行治疗干预以防止慢性炎症过程重新开始以及随后需要进一步手术的纤维化。
