Inhibition of the adherence of T-lymphocytes to epithelial cells by a cyclic peptide derived from inserted domain of lymphocyte function-associated antigen-1.
Inhibition of the adherence of T-lymphocytes to epithelial cells by a cyclic peptide derived from inserted domain of lymphocyte function-associated antigen-1.
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源自淋巴细胞功能相关抗原 1 插入结构域的环肽抑制 T 淋巴细胞与上皮细胞的粘附。
DOI：
10.1023/a:1011044616170
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发表时间：
2001
期刊：
影响因子：
5.1
通讯作者：
Siahaan,TJ
中科院分区：
文献类型：
--
作者：
Yusuf-Makagiansar,H;Makagiansar,IT;Siahaan,TJ
组织炎症的特征是炎症部位的白细胞浸润加剧。该机制需要白细胞粘附分子及其配体在发炎组织中的相互作用。在本研究中，我们证明源自 LFA-1“插入”结构域或 I 结构域的环肽 cLAB.L [cyclo1, 12-PenITDGEATDSGC] 能够抑制 T 淋巴细胞与上皮细胞单层的粘附。这种抑制被认为涉及 LFA-1/ICAM-1 相互作用的破坏。用针对粘附分子的单克隆抗体 (MAb) 或 cLAB.L 肽处理单层细胞后，佛波酯激活的 Molt-3 细胞和 IFN-γ 诱导的 Caco-2 单层细胞的异型粘附受到抑制。 MAb 可以以浓度依赖性方式抑制 ICAM-1、ICAM-2、VCAM-1 和 cLAB.L 肽的粘附。然而，这些分子的单独使用都没有导致完全抑制。低温和缺乏细胞活化会大大降低 cLAB.L 的抑制活性。 cLAB.L 肽的治疗可能会引发激活的 Molt-3 细胞的早期凋亡事件，但不会引发未激活的 Molt-3 细胞的凋亡；在 Caco-2 细胞上没有发现肽诱导细胞凋亡的迹象。总而言之，这项工作的数据表明 cLAB.L 可能可用于在组织炎症期间指导细胞靶向递送。
Tissue inflammation is characterized by aggravated leukocyte infiltration into the sites of inflammation. The mechanism requires the interactions of leukocyte adhesion-molecules and their ligands in the inflamed tissues. In this study, we demonstrate that a cyclic peptide cLAB.L [cyclo1, 12-PenITDGEATDSGC], derived from the "inserted" or I-domain of LFA-1 is able to inhibit the adherence of T-lymphocytes to the epithelial cell monolayers. This inhibition has been thought to involve the disruption of LFA-1/ICAM-1 interaction. The heterotypic adhesion of phorbol ester-activated Molt-3 cells and IFN-γ-induced Caco-2 monolayers was inhibited upon treatment of the monolayers with monoclonal antibodies (MAbs) to adhesion molecules or with cLAB.L peptide. The adhesion can be inhibited by MAbs to ICAM-1, ICAM-2, and VCAM-1, and cLAB.L peptide in a concentration-dependent manner. However, none of the individual uses of these molecules led to a total inhibition. The inhibitory activity of cLAB.L is greatly reduced by low temperature and the absence of cell activation. Treatment of cLAB.L peptide may trigger an early event of apoptosis on activated but not on non-activated Molt-3 cells; no indication of peptide-induced apoptosis was found on Caco-2 cells. Taken together, data from this work suggest that cLAB.L may have applications to direct cell-targeted delivery during tissue inflammation.