Platelet adhesion to multimerin 1 in vitro: influences of platelet membrane receptors, von Willebrand factor and shear.
BACKGROUND
Multimerin 1 (MMRN1) is a large, homopolymeric adhesive protein, stored in platelets and endothelium, that when released, binds to activated platelets, endothelial cells and the extracellular matrix.


OBJECTIVE
The goals of our study were to determine if (i) MMRN1 supports adhesion of resting and/or activated platelets under conditions of blood flow, and (ii) if MMRN1 enhances platelet adhesion to types I and III collagen.


METHODS
Platelet adhesion was evaluated using protein-coated microcapillaries, with or without added adhesive proteins and receptor antibodies. Platelets from healthy controls, Glanzmann thrombasthenia (GT) and severe von Willebrand factor (VWF)-deficient donors were tested.


RESULTS
MMRN1 supported the adhesion of activated, but not resting, washed platelets over a wide range of shear rates. At low shear (150 s(-1)), this adhesion was supported by integrins alphavbeta3 and glycoprotein (GP) Ibalpha but it did not require integrins alphaIIbbeta3 or VWF. At high shear (1500 s(-1)), adhesion to MMRN1 was supported by beta3 integrin-independent mechanisms, involving GPIbalpha and VWF, that did not require platelet activation when VWF was perfused over MMRN1 prior to platelets. MMRN1 bound to types I and III collagen, independent of VWF, however, its enhancing effects on platelet adhesion to collagen at high shear were VWF dependent.


CONCLUSIONS
MMRN1 supports platelet adhesion by VWF-dependent and -independent mechanisms that vary by flow rate. Additionally, MMRN1 binds to, and enhances, platelet adhesion to collagen. These findings suggest that MMRN1 could function as an adhesive ligand that promotes platelet adhesion at sites of vascular injury.
Tasneem
S
S
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Adam
F
F
Minullina
I
I
Pawlikowska
M
M
Hui
S K
SK
Zheng
S
S
Miller
J L
JL
Hayward
C P M
CP
D001792:Blood Platelets / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D006801:Humans; D010477:Perfusion; D010973:Platelet Adhesiveness; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013915:Thrombasthenia / Q000097:blood; D014842:von Willebrand Diseases / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism*
D001798:Blood Proteins; D024042:Collagen Type I; D024061:Collagen Type III; D011956:Receptors, Cell Surface; C069282:multimerin; D014841:von Willebrand Factor