Efficient inhibition of collagen-induced platelet activation and adhesion by LAIR-2, a soluble Ig-like receptor family member.
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); IC(50) = 18 microg/ml) and high shear rate (1500 s(-1); IC(50) = 30 microg/ml). Additional experiments revealed that LAIR-2/Fc leaves interactions between collagen and alpha2beta1 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.
Lenting
Peter J
PJ
Institut National de la Santé et de la Recherche Médicale (INSERM) U770 & Univ Paris-Sud, Le Kremlin-Bicêtre, France.
Westerlaken
Geertje H A
GH
Denis
Cécile V
CV
Akkerman
Jan Willem
JW
Meyaard
Linde
L
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D016466:CHO Cells; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D019169:Jurkat Cells; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D014841:von Willebrand Factor / Q000378:metabolism
C431503:LAIR-2 receptor; D010980:Platelet Membrane Glycoproteins; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor; D003094:Collagen