Carboxypeptidase cathepsin X mediates β2-integrin-dependent adhesion of differentiated U-937 cells

被引:68
作者
Obermajer, Natasa
Premzl, Ales
Bergant, Tina Zavasnik
Turk, Boris
Kos, Janko
机构
[1] Univ Ljubljana, Fac Pharm, SI-1000 Ljubljana, Slovenia
[2] Jozef Stefan Inst, Dept Biochem & Mol Biol, Ljubljana, Slovenia
关键词
cathepsin X; integrin; adhesion; macrophage; phagocytosis;
D O I
10.1016/j.yexcr.2006.04.019
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cathepsin X is a lysosomal carboxypeptidase with a potential role in processes of inflammation and immune response. The integrin-binding motifs RGD and ECD, present in the pro- and in mature forms of cathepsin X, respectively, suggest that this enzyme might have a function in cell signaling and adhesion. In this study, we report that cysteine protease inhibitors E-64 and CA-074 and 2F12 monoclonal antibody, all of which inhibit cathepsin X activity, significantly reduced adhesion of differentiated U-937 cells to polystyrene- and fibrinogen-coated surfaces via Mac-l integrin receptor, whereas their binding to vitronectin, fibronectin or Matrigel was not affected. On the other hand, cathepsin X, added to differentiating U-937 cells, stimulated their adhesion. Using confocal microscopy, we demonstrated that the pro-form of cathepsin X was co-localized with beta(2) and beta(3) integrin subunits and its mature form solely with the beta(2) integrin subunit with the most intense signal in cell-cell junctions in differentiated U-937 cells and in co-cultures with endothelial cells. Our results indicate that active cathepsin X mediates the function Of 2 integrin receptors during cell adhesion and that it could also be involved in other processes associated with beta(2) integrin receptors such as phagocytosis and T cell activation. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:2515 / 2527
页数:13
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共 50 条
[1]   5-(3-CARBOXYMETHOXYPHENYL)-2-(4,5-DIMETHYLTHIAZOLYL)-3-(4-SULFOPHENYL)TETRAZOLIUM, INNER SALT (MTS) AND RELATED ANALOGS OF 3-(4,5-DIMETHYLTHIAZOLYL)-2,5-DIPHENYLTETRAZOLIUM BROMIDE (MTT) REDUCING TO PURPLE WATER-SOLUBLE FORMAZANS AS CELL-VIABILITY INDICATORS [J].
BARLTROP, JA ;
OWEN, TC ;
CORY, AH ;
CORY, JG .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1991, 1 (11) :611-&
[2]   A molecular mechanism of integrin crosstalk:: αvβ3 suppression of calcium/calmodulin-dependent protein kinase II regulates α5β1 function [J].
Blystone, SD ;
Slater, SE ;
Williams, MP ;
Crow, MT ;
Brown, EJ .
JOURNAL OF CELL BIOLOGY, 1999, 145 (04) :889-897
[3]   Nanoparticles in cancer therapy and diagnosis [J].
Brigger, I ;
Dubernet, C ;
Couvreur, P .
ADVANCED DRUG DELIVERY REVIEWS, 2002, 54 (05) :631-651
[4]   REQUIREMENT OF VASCULAR INTEGRIN ALPHA(V)BETA(3) FOR ANGIOGENESIS [J].
BROOKS, PC ;
CLARK, RAF ;
CHERESH, DA .
SCIENCE, 1994, 264 (5158) :569-571
[5]   Cathepsins K, L, B, X and W are differentially expressed in normal and chronically inflamed gastric mucosa [J].
Bühling, F ;
Peitz, U ;
Krüger, S ;
Küster, D ;
Vieth, M ;
Gebert, I ;
Roessner, A ;
Weber, E ;
Malfertheiner, P ;
Wex, T .
BIOLOGICAL CHEMISTRY, 2004, 385 (05) :439-445
[6]  
Capo C, 1999, J IMMUNOL, V163, P6078
[7]   Poly(lactide-co-glycolide) nanoparticles as a carrier system for delivering cysteine protease inhibitor cystatin into tumor cells [J].
Cegnar, M ;
Premzl, A ;
Zavasnik-Bergant, V ;
Kristl, J ;
Kos, J .
EXPERIMENTAL CELL RESEARCH, 2004, 301 (02) :223-231
[8]   Kininogenase activity by the major cysteinyl proteinase (Cruzipain) from Trypanosoma cruzi [J].
DelNery, E ;
Juliano, MA ;
Lima, APCA ;
Scharfstein, J ;
Juliano, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (41) :25713-25718
[9]  
Dessaint J P, 1979, J Immunopharmacol, V1, P399
[10]   ICAM-1 (CD54) - A COUNTER-RECEPTOR FOR MAC-1 (CD11B CD18) [J].
DIAMOND, MS ;
STAUNTON, DE ;
DEFOUGEROLLES, AR ;
STACKER, SA ;
GARCIAAGUILAR, J ;
HIBBS, ML ;
SPRINGER, TA .
JOURNAL OF CELL BIOLOGY, 1990, 111 (06) :3129-3139