Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo.

TY - JOUR

T1 - Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo.

AU - Grüner, Sabine

AU - Prostredna, Miroslava

AU - Schulte, Valerie

AU - Krieg, Thomas

AU - Eckes, Beate

AU - Brakebusch, Cord

AU - Nieswandt, Bernhard

N1 - Keywords: Animals; Carotid Artery Injuries; Endothelium, Vascular; Extracellular Matrix; Hemorheology; Integrin alpha2beta1; Integrin alpha5beta1; Integrin alpha6beta1; Integrins; Ligands; Mice; Mice, Knockout; Microscopy, Video; Platelet Adhesiveness; Platelet Glycoprotein GPIIb-IIIa Complex; Platelet Membrane Glycoproteins; Thrombosis

PY - 2003

Y1 - 2003

N2 - Damage to the integrity of the vessel wall results in exposure of the subendothelial extracellular matrix (ECM), which triggers integrin-dependent adhesion and aggregation of platelets. The role of platelet beta1 integrins in these processes remains mostly undefined. Here, we demonstrate by intravital fluorescence microscopy that platelet adhesion and thrombus growth on the exposed ECM of the injured carotid artery is not significantly altered in alpha2-null mice and even in mice with a Cre/loxP-mediated loss of all beta1 integrins on their platelets. In contrast, inhibition of alphaIIbbeta3 integrin on platelets in wild-type mice blocked aggregate formation and reduced platelet adhesion by 60.0%. Strikingly, alphaIIbbeta3 inhibition had a comparable effect in alpha2-null mice, demonstrating that other receptors mediate shear-resistant adhesion in the absence of functional alpha2beta1 and alphaIIbbeta3. These were identified to be alpha5beta1 and/or alpha6beta1 as alphaIIbbeta3 inhibition abrogated platelet adhesion in beta1-null mice. We conclude that shear-resistant platelet adhesion on the injured vessel wall in vivo is a highly integrated process involving multiple integrin-ligand interactions, none of which by itself is essential.

AB - Damage to the integrity of the vessel wall results in exposure of the subendothelial extracellular matrix (ECM), which triggers integrin-dependent adhesion and aggregation of platelets. The role of platelet beta1 integrins in these processes remains mostly undefined. Here, we demonstrate by intravital fluorescence microscopy that platelet adhesion and thrombus growth on the exposed ECM of the injured carotid artery is not significantly altered in alpha2-null mice and even in mice with a Cre/loxP-mediated loss of all beta1 integrins on their platelets. In contrast, inhibition of alphaIIbbeta3 integrin on platelets in wild-type mice blocked aggregate formation and reduced platelet adhesion by 60.0%. Strikingly, alphaIIbbeta3 inhibition had a comparable effect in alpha2-null mice, demonstrating that other receptors mediate shear-resistant adhesion in the absence of functional alpha2beta1 and alphaIIbbeta3. These were identified to be alpha5beta1 and/or alpha6beta1 as alphaIIbbeta3 inhibition abrogated platelet adhesion in beta1-null mice. We conclude that shear-resistant platelet adhesion on the injured vessel wall in vivo is a highly integrated process involving multiple integrin-ligand interactions, none of which by itself is essential.

U2 - 10.1182/blood-2003-05-1391

DO - 10.1182/blood-2003-05-1391

M3 - Journal article

C2 - 12893753

SN - 0006-4971

VL - 102

SP - 4021

EP - 4027

JO - Blood

JF - Blood

IS - 12

ER -