Efficient Inhibition of Collagen-Induced Platelet Activation and Adhesion by LAIR-2, a Soluble Ig-Like Receptor Family Member |
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| Authors: | Peter J. Lenting Geertje H. A. Westerlaken Cécile V. Denis Jan Willem Akkerman Linde Meyaard |
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| Affiliation: | 1. Institut National de la Santé et de la Recherche Médicale (INSERM) U770 & Univ Paris-Sud, Le Kremlin-Bicêtre, France.; 2. Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.; 3. Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.;Indiana University, United States of America |
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| Abstract: | LAIR-1 (Leukocyte Associated Ig-like Receptor -1) is a collagen receptor that functions as an inhibitory receptor on immune cells. It has a soluble family member, LAIR-2, that also binds collagen and can interfere with LAIR-1/collagen interactions. Collagen is a main initiator for platelet adhesion and aggregation. Here, we explored the potential of soluble LAIR proteins to inhibit thrombus formation in vitro. LAIR-2/Fc but not LAIR-1/Fc inhibited collagen-induced platelet aggregation. In addition, LAIR-2/Fc also interfered with platelet adhesion to collagen at low shear rate (300 s−1; IC50 = 18 µg/ml) and high shear rate (1500 s−1; IC50 = 30 µg/ml). Additional experiments revealed that LAIR-2/Fc leaves interactions between collagen and α2β1 unaffected, but efficiently prevents binding of collagen to Glycoprotein VI and von Willebrand factor. Thus, LAIR-2/Fc has the capacity to interfere with platelet-collagen interactions mediated by Glycoprotein VI and the VWF/Glycoprotein Ib axis. |
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