Synthetic fibronectin peptides suppress arthritis in rats by interrupting leukocyte adhesion and recruitment.
Synthetic fibronectin peptides suppress arthritis in rats by interrupting leukocyte adhesion and recruitment.
复制标题
合成纤连蛋白肽通过中断白细胞粘附和募集来抑制大鼠关节炎。
DOI：
10.1172/jci117382
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
McCarthy,JB
中科院分区：
文献类型：
--
作者：
Wahl,SM;Allen,JB;Hines,KL;Imamichi,T;Wahl,AM;Furcht,LT;McCarthy,JB
在关节炎的实验模型中，白细胞粘附增加与急性和慢性滑膜炎症的演变相关。对照动物的外周血单核细胞（PBMC）与纤连蛋白基质的结合最低，而接受关节病剂量的细菌细胞壁的动物的PBMC表现出整合素mRNA表达增加和粘附增强。为了确定这种增强的粘附是否是滑膜病理学发展的原因，将从几个纤连蛋白结构域合成的肽（其在体外抑制白细胞粘附）以游离肽或与载体分子偶联的形式给予关节炎动物。不仅含有RGD或CS-1细胞结合结构域的肽抑制慢性滑膜病理（未处理动物的关节指数= 10.5 +/-0.3，而RGD为1.25 +/-0.25，CS-1为2.5 +/-0.7），但也发现从纤连蛋白的羧基末端33-kD肝素结合结构域合成的三种肽显著抑制白细胞募集和关节炎的发展。这些数据首次探索了肝素结合纤连蛋白肽在慢性炎症中的治疗潜力，基于这些数据，纤连蛋白肽对细胞粘附和募集的拮抗作用可能为调节多步粘附过程和减弱异常炎症反应提供了重要机制。图片
In an experimental model of arthritis, increased leukocyte adhesion is associated with the evolution of acute and chronic synovial inflammation. Whereas peripheral blood mononuclear cells (PBMC) from control animals bind minimally to fibronectin matrices, PBMC from animals receiving arthropathic doses of bacterial cell walls demonstrate increased integrin mRNA expression and enhanced adhesion. To determine whether this augmented adhesion was causal in the development of synovial pathology, peptides synthesized from several fibronectin domains which inhibited leukocyte adhesion in vitro were administered to arthritic animals either as free peptides or coupled to a carrier molecule. Not only were peptides containing either the RGD or CS-1 cell-binding domains inhibitory to chronic synovial pathology (articular index = 10.5 +/- 0.3 for untreated animals compared to 1.25 +/- 0.25 for RGD and 2.5 +/- 0.7 for CS-1), but three peptides synthesized from the carboxy-terminal 33-kD heparin-binding domain of fibronectin were also found to significantly inhibit leukocyte recruitment and the evolution of arthritis. Based on these data, which are the first to explore the therapeutic potential of heparin-binding fibronectin peptides in chronic inflammation, it appears that antagonism of cellular adhesion and recruitment by fibronectin peptides may provide an important mechanism for modulating the multi-step adhesion process and attenuating aberrant inflammatory responses.Images