Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
NTU Institute for Health Technologies, Interdisciplinary Graduate School, Nanyang Technological University, Singapore, Singapore.
Sci Rep. 2017 Sep 11;7(1):11201. doi: 10.1038/s41598-017-11464-x.
Host defence peptides (HDPs) derived from the C-terminus of thrombin are proteolytically generated by enzymes released during inflammation and wounding. In this work, we studied the effects of the prototypic peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), on neutrophil functions. In vitro, GKY25 was shown to decrease LPS-induced neutrophil activation. In addition, the peptide induced CD62L shedding on neutrophils without inducing their activation. Correspondingly, GKY25-treated neutrophils showed reduced attachment and rolling behaviour on surfaces coated with the CD62L ligand E-selectin. The GKY25-treated neutrophils also displayed a dampened chemotactic response against the chemokine IL-8. Furthermore, in vivo, mice treated with GKY25 exhibited a reduced local ROS response against LPS. Taken together, our results show that GKY25 can modulate neutrophil functions in vitro and in vivo.
宿主防御肽（HDPs）来源于凝血酶的 C 端，是由炎症和创伤期间释放的酶蛋白水解生成的。在这项工作中，我们研究了原型肽 GKY25（GKYGFYTHVFRLKKWIQKVIDQFGE）对中性粒细胞功能的影响。体外实验表明，GKY25 可降低 LPS 诱导的中性粒细胞激活。此外，该肽诱导 CD62L 脱落而不诱导其激活。相应地，GKY25 处理的中性粒细胞在涂有 CD62L 配体 E-选择素的表面上表现出减少的附着和滚动行为。GKY25 处理的中性粒细胞对趋化因子 IL-8 的趋化反应也减弱。此外，在体内，用 GKY25 处理的小鼠对 LPS 的局部 ROS 反应降低。总之，我们的结果表明，GKY25 可以调节体外和体内的中性粒细胞功能。
