P-Selectin Cross-Links PSGL-1 and Enhances Neutrophil Adhesion to Fibrinogen and ICAM-1 in a Src Kinase-Dependent, but GPCR-Independent Mechanism

	P-Selectin Cross-Links PSGL-1 and Enhances Neutrophil Adhesion to Fibrinogen and ICAM-1 in a Src Kinase-Dependent, but GPCR-Independent Mechanism
	Xu, T; Zhang, L; Geng, ZH; Wang, HB; Wang, JT; Chen, M; Geng, JG
刊名	CELL ADHESION & MIGRATION
	2007
卷号	1 期号:3 页码:115-123
关键词	P-selectin (CD62P) P-selectin glycoprotein ligand-1 (PSGL-1) integrins G protein-coupled receptor (GPCR) human neutrophils cell adhesion
通讯作者	Geng, JG (reprint author), Univ Minnesota, Sch Med, Dept Med, Vasc Biol Ctr, Minneapolis, MN 55455 USA.,genglab@gmail.com
英文摘要	Endothelial and platelet P-selectin (CD62P) and leukocyte integrin alpha(M)beta(2) (CD11bCD18, Mac-1) are cell adhesion molecules essential for host defense and innate immunity. Upon inflammatory challenges, P-selectin binds to PSGL-1 (P-selectin glycoprotein ligand-1, CD162) to mediate neutrophil rolling, during which integrins become activated by extracellular stimuli for their firm adhesion in a G-protein coupled receptor (GPCR)-dependent mechanism. Here we show that cross-linking of PSGL-1 by dimeric or multimeric forms of platelet P-selectin, P-selectin receptor-globulin, anti-PSGL-1 mAb and its F(ab')(2) induced adhesion of human neutrophils to fibrinogen (Fg) and intercellular cell adhesion molecule-1 (ICAM-1, CD54) and triggered a moderate clustering of alpha(M)beta(2), but monomeric forms of soluble P-selectin and anti-PSGL-1 Fab did not. Interestingly, P-selectin did not induce a detectable interleukine-8 (IL-8) secretion (<0.1 ng/ml) in 30 minutes, whereas a high concentration of IL-8 (>50 ng/ml) was required to increase neutrophil adhesion to Fg. P-selectin-induced neutrophil adhesion was significantly inhibited by PP2 (a Src kinase inhibitor), but not by pertussis toxin (PTX; a GPCR inhibitor). Activated platelets also increased neutrophil binding to fibrinogen and triggered tyrosine phosphorylation of cellular proteins. Our results indicate that P-selectin-induced integrin activation (Src kinase-dependent) is distinct from that elicited by cytokines, chemokines, chemoattractants (GPCR-dependent), suggesting that these two signal transduction pathways may cooperate for maximal activation of leukocyte integrins.
学科主题	Cell Biology
类目[WOS]	Cell Biology
收录类别	SCI
语种	英语
WOS记录号	WOS:000208233100001
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1539]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Xu, T,Zhang, L,Geng, ZH,et al. P-Selectin Cross-Links PSGL-1 and Enhances Neutrophil Adhesion to Fibrinogen and ICAM-1 in a Src Kinase-Dependent, but GPCR-Independent Mechanism[J]. CELL ADHESION & MIGRATION,2007,1(3):115-123.
APA	Xu, T.,Zhang, L.,Geng, ZH.,Wang, HB.,Wang, JT.,...&Geng, JG.(2007).P-Selectin Cross-Links PSGL-1 and Enhances Neutrophil Adhesion to Fibrinogen and ICAM-1 in a Src Kinase-Dependent, but GPCR-Independent Mechanism.CELL ADHESION & MIGRATION,1(3),115-123.
MLA	Xu, T,et al."P-Selectin Cross-Links PSGL-1 and Enhances Neutrophil Adhesion to Fibrinogen and ICAM-1 in a Src Kinase-Dependent, but GPCR-Independent Mechanism".CELL ADHESION & MIGRATION 1.3(2007):115-123.