Kriegsmann J, Keyszer G M, Geiler T, Bräuer R, Gay R E, Gay S
Department of Medicine, University of Alabama at Birmingham.
Lab Invest. 1995 Feb;72(2):209-14.
Vascular cell adhesion molecule-1 (VCAM-1) is expressed in synovial tissue of patients with rheumatoid arthritis. VCAM-1-protein has been demonstrated in nonvascular cells beside a vascular expression of this molecule. There are conflicting results about the nonvascular cell types expressing VCAM-1.
For the evaluation of VCAM-1 expression in rheumatoid synovium, this molecule has been demonstrated by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Furthermore, VCAM-1 mRNA has been demonstrated by in situ hybridization to evaluate de novo synthesis of this molecule in vivo. To elucidate the nature of the cell types expressing VCAM-1 mRNA, this molecule has been shown by combined in situ hybridization for VCAM-1 and immunohistochemistry in the same tissue section. Double labeling has been performed with anti-collagen type IV monoclonal antibodies to delineate endothelial cells and pericytes and with anti-CD68 antibodies to elucidate the expression of VCAM-1 mRNA in fibroblast-like (type B) or macrophage-like (type A) synoviocytes.
Although it has been reported that VCAM-1 occurs on endothelial cells after cytokine stimulation, we show that vascular expression of VCAM-1 mRNA and protein was minimal and restricted to small vessels beneath the lining cell layer. Further expression of VCAM-1 mRNA could be demonstrated in pericytes outside the collagen type IV containing vascular basement membrane. With respect to the expression of VCAM-1 in the synovial lining layer, we could clearly demonstrate by combined in situ hybridization and immunohistochemistry that CD68 positive cells of the monocyte/macrophage lineage in the lining layer (type A cells) do not express VCAM-1 mRNA and that the expression of VCAM-1 mRNA in the lining layer was restricted to fibroblast-like synoviocytes (type B cells). Scattered stromal cells revealing VCAM-1 mRNA were also CD68 negative.
The strong expression of VCAM-1 in the fibroblast-like cells of RA synovium and the lack of expression in the vascular endothelium suggest that the major role of VCAM-1 appears to be associated with the proliferating synovial cells prone to attach and subsequently invade articular cartilage.
血管细胞黏附分子-1（VCAM-1）在类风湿关节炎患者的滑膜组织中表达。除了该分子的血管表达外，在非血管细胞中也已证实存在VCAM-1蛋白。关于表达VCAM-1的非血管细胞类型，存在相互矛盾的结果。
为评估类风湿滑膜中VCAM-1的表达，采用碱性磷酸酶抗碱性磷酸酶（APAAP）技术证实了该分子的存在。此外，通过原位杂交证实了VCAM-1 mRNA的存在，以评估该分子在体内的从头合成。为阐明表达VCAM-1 mRNA的细胞类型的性质，在同一组织切片中通过VCAM-1原位杂交与免疫组织化学相结合的方法显示了该分子。使用抗IV型胶原单克隆抗体进行双重标记以区分内皮细胞和周细胞，并使用抗CD68抗体阐明VCAM-1 mRNA在成纤维细胞样（B型）或巨噬细胞样（A型）滑膜细胞中的表达。
尽管已有报道称细胞因子刺激后VCAM-1出现在内皮细胞上，但我们发现VCAM-1 mRNA和蛋白的血管表达极少，且仅限于衬里细胞层下方的小血管。在含IV型胶原的血管基底膜外的周细胞中可进一步证实VCAM-1 mRNA的表达。关于VCAM-1在滑膜衬里层中的表达，通过原位杂交与免疫组织化学相结合的方法，我们可以清楚地证明衬里层中单核细胞/巨噬细胞系的CD68阳性细胞（A型细胞）不表达VCAM-1 mRNA，且衬里层中VCAM-1 mRNA的表达仅限于成纤维细胞样滑膜细胞（B型细胞）。显示VCAM-1 mRNA的散在基质细胞也为CD68阴性。
VCAM-1在类风湿滑膜的成纤维细胞样细胞中强烈表达，而在血管内皮中缺乏表达，这表明VCAM-1的主要作用似乎与易于附着并随后侵入关节软骨的增殖性滑膜细胞有关。
