Di Girolamo N, Tedla N, Lloyd A, Wakefield D
Inflammation Research Unit, School of Pathology, The University of New South Wales, Sydney, Australia.
Eur J Immunol. 1998 Jun;28(6):1773-84. doi: 10.1002/(SICI)1521-4141(199806)28:06<1773::AID-IMMU1773>3.0.CO;2-B.
Matrix metalloproteinases (MMP) are proteolytic enzymes that play a key role in tissue remodelling during physiological and pathological processes, by initiating the degradation of extracellular matrix. MMP overexpression can lead to tissue destruction which is characteristic of chronic inflammatory diseases such as rheumatoid arthritis and scleritis. Plasma cells are often abundant at such sites of chronic inflammation. In the present study we investigated whether plasma cells could contribute to matrix degradation by their expression of MMP In situ hybridization and immunohistochemical analyses on diseased synovial and scleral tissue demonstrated the expression of stromelysin-1 (MMP-3) and gelatinase B (MMP-9), but little or no tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) mRNA, by IgG-positive plasma cells. Northern blot analysis of RNA extracted from a human plasma cell line (ARH-77), Epstein-Barr virus-transformed B cells, and purified peripheral blood B cells, demonstrated expression of stromelysin mRNA. TIMP-1 mRNA was only detected by the more sensitive reverse transcription PCR method in these cell types. Plasma cells and B lymphocytes cultured in the presence of monensin demonstrated cytoplasmic gelatinase B. Gelatin and casein zymography on conditioned media (CM) derived from cytokine treated plasma cells revealed the induction of secreted gelatinase and stromelysin activity. Western blotting confirmed the presence of stromelysin-1 and TIMP-1 proteins in plasma cell CM. These data suggest that plasma cells are not only capable of modulating an inflammatory response by antibody and cytokine production, but also by their ability to produce MMP. Secretion of MMP from focal aggregates of plasma cells may play a critical role in tissue destructive diseases such as rheumatoid synovitis and scleritis.
基质金属蛋白酶（MMP）是蛋白水解酶，在生理和病理过程中的组织重塑中起关键作用，通过启动细胞外基质的降解。MMP的过度表达可导致组织破坏，这是类风湿性关节炎和巩膜炎等慢性炎症性疾病的特征。浆细胞在这种慢性炎症部位通常大量存在。在本研究中，我们调查了浆细胞是否可通过其MMP的表达促进基质降解。对患病滑膜和巩膜组织进行原位杂交和免疫组化分析显示，IgG阳性浆细胞表达基质溶解素-1（MMP-3）和明胶酶B（MMP-9），但基质金属蛋白酶组织抑制剂1（TIMP-1）mRNA很少或没有表达。对从人浆细胞系（ARH-77）、爱泼斯坦-巴尔病毒转化的B细胞和纯化的外周血B细胞中提取的RNA进行Northern印迹分析，显示了基质溶解素mRNA的表达。在这些细胞类型中，仅通过更敏感的逆转录PCR方法检测到TIMP-1 mRNA。在莫能菌素存在下培养的浆细胞和B淋巴细胞显示出细胞质明胶酶B。对细胞因子处理的浆细胞的条件培养基（CM）进行明胶和酪蛋白酶谱分析，揭示了分泌的明胶酶和基质溶解素活性的诱导。蛋白质印迹法证实浆细胞CM中存在基质溶解素-1和TIMP-1蛋白。这些数据表明，浆细胞不仅能够通过产生抗体和细胞因子来调节炎症反应，还能够通过其产生MMP的能力来调节炎症反应。浆细胞局部聚集分泌MMP可能在类风湿性滑膜炎和巩膜炎等组织破坏性疾病中起关键作用。
