Fava R A, Olsen N J, Postlethwaite A E, Broadley K N, Davidson J M, Nanney L B, Lucas C, Townes A S
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
J Exp Med. 1991 May 1;173(5):1121-32. doi: 10.1084/jem.173.5.1121.
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 microgram 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. [3H]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.
我们研究了将人重组转化生长因子β1（hrTGF-β1）引入大鼠滑膜组织的后果，以便更好地理解在人类关节炎滑膜积液中发现生物活性TGF-β这一事实的意义。在向大鼠膝关节内注射1微克hrTGF-β1后的4 - 6小时内，观察到多形核白细胞（PMN）大量募集。采用细胞化学和高分辨率组织学技术对PMN的流入进行定量，其在注射后6小时达到峰值。在博伊登小室试验中，1 - 10 fg/ml的hrTGF-β1引起的PMN趋化反应比FMLP引起的反应更强，这表明TGF-β1在体外和体内都是PMN的有效趋化剂。体外佛波酯肉豆蔻酸酯乙酸盐刺激脱颗粒过程中储存的TGF-β1被分泌，这有力地表明PMN可能是炎症浸润中TGF-β的重要来源。通过ELISA检测，人PMN的酸/乙醇提取物中，每10⁹个细胞平均含有355 ng的TGF-β1，这些TGF-β1在PMN脱颗粒过程中可能被分泌。体内[³H]胸腺嘧啶核苷掺入和组织切片放射自显影显示，TGF-β1注射引发了广泛的细胞增殖。滑膜衬里细胞和位于滑膜下结缔组织深处的细胞被确定为至少部分参与TGF-β1诱导增生的新细胞的来源。我们的结果表明，TGF-β能够对滑膜组织产生致病作用，并且PMN可能是滑膜积液中TGF-β的重要来源。
