Shin Kichul, Gurish Michael F, Friend Daniel S, Pemberton Alan D, Thornton Elisabeth M, Miller Hugh R, Lee David M
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Arthritis Rheum. 2006 Sep;54(9):2863-71. doi: 10.1002/art.22058.
Mast cells (MCs) are a heterogeneous population of tissue-resident bone marrow-derived cells; distinct MC subpopulations are situated at specific microanatomic locations. The phenotype of the murine synovial MC remains undefined. Since MCs have been implicated in the pathogenesis of inflammatory arthritis, we sought to define the phenotype of the murine synovial MC population in normal and arthritic joints. We also examined the contribution of lymphocytes to synovial MC physiology.
The MC phenotype in healthy and K/BxN serum transfer-induced arthritic synovial tissue was defined using immunohistochemical staining of prototypic MC-specific proteases (murine MC proteases [mMCP] 1, 2, 4, 5, 6, and 7) (chymases and tryptases). MC numbers and density were determined by histomorphometry in healthy and arthritic synovia. The lymphocyte contribution to MC populations was assessed using RAG-null mice.
We found that synovial MCs display a connective tissue mast cell (CTMC) phenotype in both normal and arthritic synovial tissue, which expresses mMCP-4, -5, -6, and -7, but not mMCP-1 or mMCP-2. In addition, MC hyperplasia was seen in the arthritic synovium. In RAG-null mice, the phenotype and degree of MC hyperplasia were identical to those observed in normal mice with and without arthritis. Furthermore, in contrast to skin CTMCs, all synovial MCs expressed mMCP-6, demonstrating discrete differences between synovial CTMCs and other anatomic CTMC populations.
Our findings demonstrate that the murine synovial MC population is composed of lymphocyte-independent CTMCs and identify arthritic synovium as a model system by which to gain insight into the poorly understood physiology of CTMCs in chronic inflammation.
肥大细胞（MCs）是一类源自骨髓的异质性组织驻留细胞；不同的MC亚群位于特定的微观解剖位置。小鼠滑膜MC的表型尚未明确。由于MCs与炎性关节炎的发病机制有关，我们试图确定正常和关节炎关节中小鼠滑膜MC群体的表型。我们还研究了淋巴细胞对滑膜MC生理学的作用。
使用原型MC特异性蛋白酶（小鼠MC蛋白酶[mMCP]1、2、4、5、6和7）（糜蛋白酶和组织蛋白酶）的免疫组织化学染色来确定健康和K/BxN血清转移诱导的关节炎滑膜组织中的MC表型。通过组织形态计量学确定健康和关节炎滑膜中的MC数量和密度。使用RAG基因敲除小鼠评估淋巴细胞对MC群体的作用。
我们发现滑膜MC在正常和关节炎滑膜组织中均表现出结缔组织肥大细胞（CTMC）表型，其表达mMCP-4、-5、-6和-7，但不表达mMCP-1或mMCP-2。此外，在关节炎滑膜中可见MC增生。在RAG基因敲除小鼠中，MC增生的表型和程度与有无关节炎的正常小鼠中观察到的相同。此外，与皮肤CTMCs不同，所有滑膜MC均表达mMCP-6，表明滑膜CTMCs与其他解剖学CTMC群体之间存在明显差异。
我们的研究结果表明，小鼠滑膜MC群体由不依赖淋巴细胞的CTMC组成，并将关节炎滑膜确定为一个模型系统，通过该系统可以深入了解慢性炎症中CTMCs尚未完全理解的生理学。
