Functional relevance during lymphocyte migration and cellular localization of activated beta 1 integrins

被引:38
作者
Gomez, M
Luque, A
delPozo, MA
Hogg, N
SanchezMadrid, F
Cabanas, C
机构
[1] UNIV COMPLUTENSE MADRID, FAC MED, DEPT BIOQUIM & BIOL MOL, MADRID, SPAIN
[2] IMPERIAL CANC RES FUND, LONDON WC2A 3PX, ENGLAND
关键词
integrin activation; ligand-induced binding site epitope; lymphocyte migration;
D O I
10.1002/eji.1830270103
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The state of integrin activation can be assessed by monoclonal antibodies (mAb) that selectively recognize integrins in their active form. We demonstrate herein that the expression of the epitope recognized by mAb HUTS-21 is induced on T lymphoblasts upon binding of soluble vascular cell adhesion molecule (VCAM)-1 and an 80-kDa tryptic fragment of fibronectin (FN80) to the beta 1 integrins very late activation antigen (VLA)-4 and VLA-5, and that this effect is dependent on ligand concentration and is specific for beta 1 integrins. On T lymphoblasts adhering to immobilized fibronectin, the HUTS-21 epitope localized exclusively to sites of integrin binding to fibronectin. These results indicate that mAb HUTS-21 recognizes a ligand-induced binding site (LIES) on the common beta 1 subunit of VLA proteins. Engagement of beta 1 integrins through this LIES epitope inhibited T lymphoblast movement on fibronectin, as determined by quantitative time-lapse video microscopy studies. Furthermore, the HUTS-21 mAb also prevented T lymphoblast-directed migration through gradients of substratum-immobilized beta 1 integrin ligands such as fibronectin or VCAM-1, whereas it did not affect migration on intercellular adhesion molecule (ICAM)-1. This anti-LIES mAb stimulated cell adhesion through postreceptor events, without affecting receptor affinity for ligand, and appears to interfere with cell migration by a mechanism distinct from that of other anti-beta 1 activating antibodies.
引用
收藏
页码:8 / 16
页数:9
相关论文
共 59 条
[1]  
ADAMS JC, 1993, DEVELOPMENT, V117, P1183
[2]   REGULATION OF THE VLA INTEGRIN LIGAND INTERACTIONS THROUGH THE BETA-1 SUBUNIT [J].
ARROYO, AG ;
SANCHEZMATEOS, P ;
CAMPANERO, MR ;
MARTINPADURA, I ;
DEJANA, E ;
SANCHEZMADRID, F .
JOURNAL OF CELL BIOLOGY, 1992, 117 (03) :659-670
[3]  
ARROYO AG, 1993, J BIOL CHEM, V268, P9863
[4]   EXPRESSION AND FUNCTIONAL-SIGNIFICANCE OF AN ACTIVATION-DEPENDENT EPITOPE OF THE BETA-1 INTEGRINS IN CHRONIC INFLAMMATORY DISEASES [J].
ARROYO, AG ;
GARCIAVICUNA, R ;
MARAZUELA, M ;
YEDNOCK, TA ;
GONZALEZAMARO, R ;
SANCHEZMADRID, F .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (06) :1720-1728
[5]   PRODUCTION OF MONOCLONAL ANTIBODIES TO GROUP-A ERYTHROCYTES, HLA AND OTHER HUMAN CELL-SURFACE ANTIGENS - NEW TOOLS FOR GENETIC-ANALYSIS [J].
BARNSTABLE, CJ ;
BODMER, WF ;
BROWN, G ;
GALFRE, G ;
MILSTEIN, C ;
WILLIAMS, AF ;
ZIEGLER, A .
CELL, 1978, 14 (01) :9-20
[6]   MOTILITY OF FIBRONECTIN RECEPTOR-DEFICIENT CELLS ON FIBRONECTIN AND VITRONECTIN - COLLABORATIVE INTERACTIONS AMONG INTEGRINS [J].
BAUER, JS ;
SCHREINER, CL ;
GIANCOTTI, FG ;
RUOSLAHTI, E ;
JULIANO, RL .
JOURNAL OF CELL BIOLOGY, 1992, 116 (02) :477-487
[7]  
BAZZONI J, 1992, J BIOL CHEM, V270, P25570
[8]   EXPOSURE OF PLATELET FIBRINOGEN RECEPTORS BY ADP AND EPINEPHRINE [J].
BENNETT, JS ;
VILAIRE, G .
JOURNAL OF CLINICAL INVESTIGATION, 1979, 64 (05) :1393-1401
[9]  
BERENDT AR, 1992, CELL, V14, P9
[10]   LIGAND INTERCELLULAR-ADHESION MOLECULE-1 HAS A NECESSARY ROLE IN ACTIVATION OF INTEGRIN LYMPHOCYTE FUNCTION-ASSOCIATED MOLECULE-1 [J].
CABANAS, C ;
HOGG, N .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (12) :5838-5842