Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (alpha 2 beta 1-integrin)

Abstract

Platelet adhesion to fibrillar collagens (types I, II, III, and V) and nonfibrillar collagens (types IV, VI, VII, and VIII) was investigated in the presence of physiologic concentrations of divalent cations under conditions of stasis and flow. Under static conditions, platelet adhesion was observed to collagen types I through VII but not to type VIII. Under flow conditions, platelet adhesion to collagen types I, II, III, and IV was almost independent of shear rates above 300/s. Collagen type V was nonadhesive. Platelet adhesion to collagen type VI was shear rate-dependent and optimal at a rate of 300/s. Collagen types VII and VIII showed minor reactivity and supported platelet adhesion only between shear rates 100 to 1,000/s. Monoclonal antibody (MoAb) 176D7, directed against platelet membrane glycoprotein Ia (GPIa; very late antigen [VLA]-alpha 2 subunit), completely inhibited platelet adhesion to all collagens tested, under conditions of both stasis and flow. Platelet adhesion to collagen type III at shear rate 1,600/s was only inhibited for 85%. The concentration of antibody required for complete inhibition of platelet adhesion was dependent on the shear rate and the reactivity of the collagen. An MoAb directed against GPIIa (VLA-beta subunit) partially inhibited platelet adhesion to collagen. These results show that GPIa-IIa is a major and universal platelet receptor for eight unique types of collagen.

A mechanism to safeguard platelet adhesion under high‐shear flow: von Willebrand factor–glycoprotein Ib and integrin α2β1–collagen interactions make complementary, collagen‐type‐specific contributions to adhesion: a rebuttal

“…In contrast to what has been described by Moroi and Jung, both collagen I and III have been shown to bind VWF [3][4][5] and the GPIba-VWF interaction has been shown to be essential for platelet adhesion to both collagen I and III at higher shear rates by multiple groups [6,7]. Integrin a 2 b 1 has been shown to be important in adhesion to both collagen I and III [8,9], which also contradicts the current data from Moroi and Jung. Indeed, specific a 2 b 1 -binding sequences have been demonstrated in collagen I (GFOGER, in which O is hydroxyproline) and III (GXXGER and GXXGEN) [10,11].…”

Platelet adhesion to multimerin 1 in vitro: influences of platelet membrane receptors, von Willebrand factor and shear

“…7A,B), suggest MMRN1 might also have roles in platelet adhesion by binding to collagen. This could be functionally important at sites of vessel injury, where types I, III and other collagens support platelet adhesion [8,40], in concert with VWF and other adhesive ligands [12], including fibronectin [41,42]. Now that MMRN1 is known to support platelet adhesion, at a variety of shear rates, and enhance platelet adhesion to collagen, information is needed on its contributions to platelet function in vivo.…”

The collagen family members as cell adhesion proteins

“…(63)(64)(65) Integrin a1b1 is a low-avidity receptor for fibril-forming collagens I-III and V (63)(64)(65) and it has been reported to recognize collagens VIII and IX. (44,68) Binding specificities of integrins a10b1 and a11b1 are less well known. (37,65) The analyses based on recombinant aI domains and transfected cells indicate that they are less selective between fibril-forming and other collagen subtypes than a1b1 or a2b1.…”