Modulation of the adhesion of neutrophils to endothelium and the expression of intercellular adhesion molecule 1 in endothelial cells by one small peptide interfering with IgG-FcγR interaction
- VernacularTitle:阻断IgG-Fcγ受体结合的短肽对粒细胞与内皮细胞黏附及内皮细胞细胞间黏附分子1表达的影响
- Author:
Xiangling WANG
;
Haijin YU
;
Hong REN
;
Weiming WANG
;
Liyan NI
;
Nan CHEN
- Publication Type:Journal Article
- Keywords:
Vasculitis;
Small peptide;
Cellular adhesion;
Intracelluar adhesion molecule 1
- From:
Chinese Journal of Nephrology
2008;24(3):162-167
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of tg19320,a small peptide,interfering with IgG-FcγR interaction on the adhesion of neutrophils to endothelium and the expression of intercellular adhesion molecule 1 (ICAM-1)in endothelial cells and its possible mechanism.Methods Tg19320 was prepared by solid-phase peptide synthesis.ANCA IgG was isolated from the serum of active ANCA-associated systemic vasculitis(AASV)patients.When primary human umbilical vein endothelial cells(HUVEC)grew into connuence in cytokine-free eonditions,the cells were stimulated with TNF-α,human normal IgG,ANCA IgG and ANCA IgG+tg19320 respectively.HUVEC were pretreated with tg19320 for 45 minutes before being stimulated by ANCA IgG.Non-activated neutrophils was added to treat HUVEC and adhesion was measured by cell count.The expression of ICAM-1 mRNA and protein was assessed by real-time PCR and Western blot respectively.Soluble ICAM-1(sICAM-1)was determined using ELISA technique.Phosphorylation of IκB-α was assessed by Western blot. Results ANCA IgG significantly up-regulated the expression of ICAM-1 in HUVEC and promoted sICAM-1 release(P＜0.05),and TNF-α enhanced the effect of ANCA.These effects were almost completely abolished by tgl9320 both at protein and mRNA level.Furthermore,ANCA IgG increased the IκB-α phosporylation in HUVEC and tg19320could inhibit the effect. Conclusions ANCA IgG can modulate the expression of ICAM-1 and sICAM-1 release in endothelial cells.FcγR probably play a critical role in the ICAM-1 expression up-regulated by ANCA,which is mediated in part through NF-κB signaling pathway.Tg19320 has protective effect on endothelium in AASV in vitro.
