A novel functional motif of osteopontin for human lymphocyte migration and survival

被引：25

作者：

Cao, Zhiguo ^{[1
,2
,3
]}

Dai, Jianxin ^{[1
,2
,3
]}

Fan, Kexin ^{[3
]}

Wang, Huajing ^{[3
]}

Ji, Guanghui ^{[3
]}

Li, Bohua ^{[3
,4
]}

Zhang, Dapeng ^{[3
,4
]}

Hou, Sheng ^{[3
,4
]}

Qian, Weizhu ^{[3
,4
]}

Zhao, Jian ^{[3
]}

Wang, Hao ^{[3
,4
]}

Guo, Yajun ^{[1
,2
,3
,4
]}

机构：

[1] Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China

[2] Jiao Tong Univ, Sch Pharm, Shanghai 200025, Peoples R China

[3] Second Mil Med Univ, Int Joint Canc Inst, Shanghai 200433, Peoples R China

[4] Shanghai Ctr Cell Engn & Antibody, Shanghai 201203, Peoples R China

来源：

MOLECULAR IMMUNOLOGY | 2008年 / 45卷 / 14期

基金：

中国国家自然科学基金;

关键词：

osteopontin; epitope; monoclonal antibody; lymphocyte migration; cell survival;

D O I：

10.1016/j.molimm.2008.06.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Osteopontin (OPN) is an extracellular matrix protein of pleiotropic properties and plays an important role in regulating lymphocyte adhesion and cytokine production associated with inflammatory processes and autoimmune diseases. Here we developed and characterized a monoclonal antibody (mAbs) (230133) specific for human OPN. This antibody could inhibit OPN-induced lymphocyte adhesion, migration and survival. Epitope mapping showed that 23C3D3 could specifically recognize the phage displayed peptide (WLNPDP48)-W-43. In addition, a synthesized mimetic peptide (mimotope) 23P ((40)VATWLNPDPSQK(51)) could block the binding of 23C3D3 to hOPN and significantly inhibit the hOPN-induced lymphocyte adhesion, migration and survival. Moreover, mutations on the WLNPDP motif of hOPN also markedly diminished its activity for lymphocyte activation. Interestingly, this novel epitope is located in the extremely retained domain in all species. The functioning assay indicates that this novel epitope is critically involved in the lymphocyte migration and survival through activating ERK and the transcription factor NF-kappa B pathway, which can be inhibited by the motif (WLNPDP48)-W-43 blocking antibody, 23C3D3. These results suggest that this novel epitope of OPN may provide a potential therapeutic target for the treatment of T cell-mediated immune diseases. (C) 2008 Elsevier Ltd. All right reserved.

引用

页码：3683 / 3692

页数：10

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