TRANSFORMING GROWTH-FACTOR BETA-1 (TGF-BETA-1) INDUCED NEUTROPHIL RECRUITMENT TO SYNOVIAL TISSUES - IMPLICATIONS FOR TGF-BETA-DRIVEN SYNOVIAL INFLAMMATION AND HYPERPLASIA
TRANSFORMING GROWTH-FACTOR BETA-1 (TGF-BETA-1) INDUCED NEUTROPHIL RECRUITMENT TO SYNOVIAL TISSUES - IMPLICATIONS FOR TGF-BETA-DRIVEN SYNOVIAL INFLAMMATION AND HYPERPLASIA
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DOI：
10.1084/jem.173.5.1121
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发表时间：
1991-05-01
影响因子：
15.3
通讯作者：
TOWNES, AS
中科院分区：
文献类型：
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作者：
FAVA, RA;OLSEN, NJ;TOWNES, AS
我们已经研究了将人重组转化生长因子β 1（hrTGF-β 1）引入大鼠滑膜组织的后果，以开始更好地理解在人关节炎滑膜渗出液中发现生物活性TGF-β这一事实的意义。在向大鼠膝关节内注射1 μ g hrTGF-β-1后4-6小时内，观察到多形核白细胞（PMN）的广泛募集。细胞化学和高分辨率的组织学技术被用来定量的流入的中性粒细胞，注射后6小时达到高峰。在Boyden室试验中，1-10 fg/ml的hrTGF-β-1引起的PMN的趋化反应的幅度大于FMLP引起的趋化反应的幅度，这表明TGF-β-1是体外和体内PMN的有效趋化剂。中性粒细胞可能是炎性浸润中TGF-β的重要来源，这一点被证实在体外佛波醇肉豆蔻酸酯刺激的脱粒过程中分泌储存的TGF-β 1所强烈暗示。通过ELISA测定的人PMN的酸/乙醇提取物含有平均355 ng TGF/β-1/10（9）个细胞，其在PMN的脱粒期间可能可用于分泌。[H-3]体内胸苷掺入和组织切片的放射自显影显示，TGF-β-1注射引发了广泛的细胞增殖。滑液衬里细胞和位于滑液下结缔组织深处的细胞被确定为至少一些导致TGF-β-1诱导增生的新细胞的来源。我们的研究结果表明，TGF-β能够对滑膜组织产生致病作用，PMN可能是滑膜积液中TGF-β的重要来源。
We have studied the consequences of introducing human recombinant transforming growth factor beta-1 (hrTGF-beta-1) into synovial tissue of the rat, to begin to better understand the significance of the fact that biologically active TGF-beta is found in human arthritic synovial effusions. Within 4-6 h after the intra-articular injection of 1-mu-g of hrTGF-beta-1 into rat knee joints, extensive recruitment of polymorphonuclear leukocytes (PMNs) was observed. Cytochemistry and high resolution histological techniques were used to quantitate the influx of PMNs, which peaked 6 h post-injection. In a Boyden chamber assay, hrTGF-beta-1 at 1-10 fg/ml elicited a chemotactic response from PMNs greater in magnitude than that evoked by FMLP, establishing that TGF-beta-1 is an effective chemotactic agent for PMNs in vitro as well as in vivo. That PMNs may represent an important source of TGF-beta in inflammatory infiltrates was strongly suggested by a demonstration that stored TGF-beta-1 was secreted during phorbol myristate acetate-stimulated degranulation in vitro. Acid/ethanol extracts of human PMNs assayed by ELISA contained an average of 355 ng of TGF/beta-1 per 10(9) cells potentially available for secretion during degranulation of PMNs.[H-3]Thymidine incorporation in vivo and autoradiography of tissue sections revealed that widespread cell proliferation was triggered by TGF-beta-1 injection. Synovial lining cells and cells located deep within the subsynovial connective tissue were identified as sources of at least some of the new cells that contribute to TGF-beta-1-induced hyperplasia. Our results demonstrate that TGF-beta is capable of exerting pathogenic effects on synovial tissue and that PMNs may represent a significant source of the TGF-beta present in synovial effusions.