Activation of the GP IIb-IIIa complex induced by platelet adhesion to collagen is mediated by both α2β1 integrin and GP VI

被引:70
作者
Nakamura, T
Kambayashi, J
Okuma, M
Tandon, NN
机构
[1] Otsuka Amer Pharmaceut Inc, Maryland Res Labs, Rockville, MD 20850 USA
[2] Takashima Gen Hosp, Shiga 5201121, Japan
关键词
D O I
10.1074/jbc.274.17.11897
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
alpha(2)beta(1) integrin, CD36, and GP VI have all been implicated in platelet-collagen adhesive interactions. We have investigated the role of these glycoproteins on activation of the GP IIb-IIIa complex induced by platelet adhesion to type I fibrillar and monomeric collagen under static conditions. In the presence of Mg2+, platelet adhesion to fibrillar collagen induced activation of the GP IIb-IIIa complex and complete spreading. Anti-alpha(2)beta(1) integrin and anti-GP VI antibodies inhibited the activation of the GP IIb-IIIa complex by about 40 and 50%, respectively, at 60 min although minimal inhibitory effects on adhesion were seen. Platelet spreading was markedly reduced by anti-alpha(2)beta(1) integrin antibody. The combination of anti-alpha(2)beta(1) integrin with anti-GP VI anti body completely inhibited both platelet adhesion and activation of the GP IIb-IIIa complex. Anti-CD36 antibody had no significant effects on platelet adhesion, spreading, and the activation of the GP IIb-IIIa complex at 60 min. Aspirin and the thromboxane A(2) receptor antagonist SQ29548 inhibited activation of the GP IIb-IIIa complex about 30% but had minimal inhibitory effect on adhesion. In the absence of Mg2+, there was significant activation of the GP IIb-IIIa complex brat minimal spreading was observed. Anti-GP VI antibody completely inhibited adhesion whereas no effect was observed with anti-alpha(2)beta(1) integrin antibody. Anti-CD36 antibody partially inhibited both adhesion and the activation of the GP IIb-IIIa complex. Platelet adhesion to monomeric collagen, which requires Mg2+ and is exclusively mediated by alpha(2)beta(1) integrin, resulted in partial activation of the GPIIb-IIIa complex and spreading. No significant effects were observed by anti-CD36 and anti-GP VI antibodies. These results suggest that both alpha(2)beta(1) integrin and GP VI are involved in inside-out signaling leading to activation of the GP IIb-IIIa complex after platelet adhesion to collagen and generation of thromboxane A(2) may further enhance expression of activated GP IIb-IIIa complexes.
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页码:11897 / 11903
页数:7
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共 50 条
[31]  
MUGGLI R, 1973, Thrombosis Research, V3, P715, DOI 10.1016/0049-3848(73)90018-2
[32]   Platelet adhesion to native type I collagen fibrils -: Role of GPVI in divalent cation-dependent and -independent adhesion and thromboxane A2 generation [J].
Nakamura, T ;
Jamieson, GA ;
Okuma, M ;
Kambayashi, J ;
Tandon, NN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (08) :4338-4344
[33]   HUMAN-BLOOD PLATELETS SHOWING NO RESPONSE TO COLLAGEN FAIL TO EXPRESS SURFACE GLYCOPROTEIN-IA [J].
NIEUWENHUIS, HK ;
AKKERMAN, JWN ;
HOUDIJK, WPM ;
SIXMA, JJ .
NATURE, 1985, 318 (6045) :470-472
[34]   Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor [J].
Polgar, J ;
Clemetson, JM ;
Kehrel, BE ;
Wiedemann, M ;
Magnenat, EM ;
Wells, TNC ;
Clemetson, KJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (21) :13576-13583
[35]   REGULATION OF CYTOSOLIC CALCIUM BY COLLAGEN IN SINGLE HUMAN PLATELETS [J].
POOLE, AW ;
WATSON, SP .
BRITISH JOURNAL OF PHARMACOLOGY, 1995, 115 (01) :101-106
[36]  
RAO GHR, 1994, J BIOL CHEM, V269, P13899
[37]   DEFICIENCY OF P62, A PUTATIVE COLLAGEN RECEPTOR, IN PLATELETS FROM A PATIENT WITH DEFECTIVE COLLAGEN-INDUCED PLATELET-AGGREGATION [J].
RYO, R ;
YOSHIDA, A ;
SUGANO, W ;
YASUNAGA, M ;
NAKAYAMA, K ;
SAIGO, K ;
ADACHI, M ;
YAMAGUCHI, N ;
OKUMA, M .
AMERICAN JOURNAL OF HEMATOLOGY, 1992, 39 (01) :25-31
[38]   DISTINCT DETERMINANTS ON COLLAGEN SUPPORT ALPHA-2-BETA-1 INTEGRIN-MEDIATED PLATELET-ADHESION AND PLATELET ACTIVATION [J].
SANTORO, SA ;
WALSH, JJ ;
STAATZ, WD ;
BARANSKI, KJ .
CELL REGULATION, 1991, 2 (11) :905-913
[39]   IDENTIFICATION OF A 160,000 DALTON PLATELET MEMBRANE-PROTEIN THAT MEDIATES THE INITIAL DIVALENT CATION-DEPENDENT ADHESION OF PLATELETS TO COLLAGEN [J].
SANTORO, SA .
CELL, 1986, 46 (06) :913-920
[40]   Integrin signaling: The platelet paradigm [J].
Shattil, SJ ;
Kashiwagi, H ;
Pampori, N .
BLOOD, 1998, 91 (08) :2645-2657