EMMPRIN (CD147) is a novel receptor for platelet GPVI and mediates platelet rolling via GPVI-EMMPRIN interaction.
The Extracellular Matrix Metalloproteinase Inducer (EMMPRIN, CD147, basigin) is an immunoglobulin-like receptor expressed in various cell types. During cellular interactions homotypic EMMPRIN-EMMPRIN interactions are known to induce the synthesis of matrix metalloproteinases. Recently, we have identified EMMPRIN as a novel receptor on platelets. To our knowledge EMMPRIN has not been shown to serve as adhesion receptor, yet. Here we characterise platelet glycoprotein VI (GPVI) as a novel adhesion receptor for EMMPRIN. Human platelets were prestimulated with ADP and perfused over immobilised recombinant EMMPRIN-Fc or Fc-fragments under arterial shear conditions. ADP-stimulated platelets showed significantly enhanced rolling (but not enhanced firm adhesion) on immobilised EMMPRIN-Fc compared to Fc. Pretreatment of platelets with blocking mAbs anti-EMMPRIN or anti-GPVI leads to a significant reduction of rolling platelets on immobilised EMMPRIN-Fc, whereas pretreatment with blocking mAbs anti-p-selectin, anti-alpha4-integrin or anti-GPIIb/IIIa complex (20 microg/ml each) had no effect. Consistently, chinese hamster ovary (CHO) cells stably transfected with GPVI showed enhanced rolling (but not adhesion) on immobilised EMMPRIN-Fc in comparison to non-transfected CHO cells. Similarly, CHO cells stably transfected with EMMPRIN showed enhanced rolling on immobilised GPVI-Fc (or EMMPRIN-Fc) compared to non transfected CHO-cells. Finally, specific binding of EMMPRIN to GPVI was demonstrated by a modified ELISA and surface plasmon resonance technology with a dissociation constant of 88 nM. Platelet GPVI is a novel receptor for EMMPRIN and can mediate platelet rolling via GPVI-EMMPRIN interaction.
Medizinische Klinik III, Universitätsklinikum Tübingen, Tübingen, Germany.
Peter
P
Seizer
Oliver
O
Borst
Harald F
HF
Langer
Andreas
A
Bültmann
Götz
G
Münch
Yared
Y
Herouy
Konstantinos
K
Stellos
Björn
B
Krämer
Boris
B
Bigalke
Berthold
B
Büchele
Max G
MG
Bachem
Dietmar
D
Vestweber
Thomas
T
Simmet
Meinrad
M
Gawaz
Andreas E
AE
May
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D051926:Basigin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D051379:Mice; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D000911:Antibodies, Monoclonal; C497886:BSG protein, human; D018955:CD36 Antigens; D019007:P-Selectin; D011993:Recombinant Fusion Proteins; D051926:Basigin; D000244:Adenosine Diphosphate