Platelet-reactive sites in collagens type I and type III. Evidence for separate adhesion and aggregatory sites

Morton, L F; Peachey, Anthony R.; Barnes, Michael J.

doi:10.1042/bj2580157

Cited by 87 publications

(66 citation statements)

References 42 publications

(60 reference statements)

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“…Inhibition of the NCX by CBDMB caused a significant de- 3 min prior to the addition of collagen. b, relative percent change in collagen-induced platelet aggregation measured 2 min following the administration of collagen (10 g/ml) to platelets administered CBDMB (4 M) or EIPA (50 M) 3 min prior to the addition of collagen compared with the control.…”

Section: Resultsmentioning

confidence: 99%

“…Collagen fibers are exposed to circulating platelets following injury to the vessel wall and play an important role in hemostasis through the creation of a physical barrier at the site of vascular damage, thereby limiting blood loss (2)(3)(4), and the stimulation of platelet activation, thereby recruiting additional platelets to the site of damage as well as consolidating the thrombus (4). The dual actions of collagen have been explained in the two-step model for activation, which suggests that adhesion and activation of platelets are mediated through the interaction of collagen with platelet integrin ␣ 2 ␤ 1 and glycoprotein VI, respectively (3, 5).…”

Section: Discussionmentioning

confidence: 99%

“…Following vascular damage, collagen is exposed to circulating platelets and both acts as a substrate for the adhesion of platelets (2-4) and induces platelet activation (4). The prevailing evidence proposes that two receptors are involved in the platelet response to collagen; integrin ␣ 2 ␤ 1 acts to adhere platelets to collagen, allowing platelets to interact with the lower affinity receptor glycoprotein VI, which is mainly responsible for platelet activation (3,5).Many of the platelet responses to collagen progress simultaneously when platelets adhere to collagen. At high concentrations, collagen activation of platelets has been shown to proceed through activation of phospholipase C␥2 and subsequent cleavage of phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and 1,2-diacylglycerol (6, 7).…”

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Mechanism of Collagen Activation in Human Platelets

Roberts

McNicol

Bose

2004

Journal of Biological Chemistry

127

110

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The mechanism of collagen-induced human platelet activation was examined using Ca 2؉ , Na ؉ , and the pHsensitive fluorescent dyes calcium green/fura red, sodium-binding benzofuran isophthalate, and 2 ,7 -bis(2-car- Collagen is the most thrombogenic component of the subendothelium (1). Following vascular damage, collagen is exposed to circulating platelets and both acts as a substrate for the adhesion of platelets (2-4) and induces platelet activation (4). The prevailing evidence proposes that two receptors are involved in the platelet response to collagen; integrin ␣ 2 ␤ 1 acts to adhere platelets to collagen, allowing platelets to interact with the lower affinity receptor glycoprotein VI, which is mainly responsible for platelet activation (3,5).Many of the platelet responses to collagen progress simultaneously when platelets adhere to collagen. At high concentrations, collagen activation of platelets has been shown to proceed through activation of phospholipase C␥2 and subsequent cleavage of phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and 1,2-diacylglycerol (6, 7). Inositol 1,4,5-trisphosphate induces the release of calcium from the dense tubular system (8, 9), whereas 1,2-diacylglycerol activates protein kinase C (10). The collagen-induced inositol 1,4,5-trisphosphate-mediated increase in [Ca 2ϩ ] i is accompanied by an influx of calcium from the extracellular milieu (11, 12). 1,2-Diacylglycerol and calcium mediate the characteristic platelet activation responses such as shape change, granule secretion, and aggregation.At lower concentrations, many of the effects of collagen are enhanced by its production of thromboxane A 2 (TXA) 1 (6, 13-15). The collagen-induced increase in [Ca 2ϩ ] i can be decreased by inhibiting the production of TXA via the pretreatment of platelets with cyclooxygenase inhibitors such as aspirin (11,16,17).Calcium is an important second messenger in the platelet activation cascade. At rest, a [Ca 2ϩ ] i of ϳ100 nM is maintained by a balance between the leak of Ca 2ϩ into the platelet and the concurrent efflux of free Ca 2ϩ across the plasma membrane of the platelet and accumulation in intracellular stores (18,19). Ca 2ϩ is moved out across the plasma membrane through the actions of the plasma membrane Ca 2ϩ -ATPase and the Na ϩ / Ca 2ϩ exchanger (NCX). Plasma membrane Ca 2ϩ -ATPases are membrane-inserted enzymes that use the energy of ATP hydrolysis to move Ca 2ϩ against its gradient and across the membrane. The NCX is capable of moving Ca 2ϩ into or out of the platelet cytosol in exchange for Na ϩ (20, 21). In the resting state, the NCX removes Ca 2ϩ from the platelet cytosol. Internally, Ca 2ϩ is transported into the dense tubular system by the sarco/endoplasmic reticulum Ca 2ϩ -ATPases 2b and 3 (22,23).In response to a moderate dose of collagen (10 g/ml), ϳ70% of the increase in [Ca 2ϩ ] i is due to the influx of Ca 2ϩ from the extracellular milieu, with the remainder as a function of Ca 2ϩ release from the dense tubular system (12). Because voltagega...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Mechanism of Collagen Activation in Human Platelets

Roberts

McNicol

Bose

2004

Journal of Biological Chemistry

127

110

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“…This is difficult to test with collagen because of its numerous recognition sequences that can interact with different receptors. In the two-step, two-receptor model (39), which is the simplest version proposed for collagen-platelet interactions in primary hemostasis, it was suggested that the platelet binds through ␣ 2 ␤ 1 first and then is activated via interactions with GPVI/Fc␥. However, platelet activation via GPVI/Fc␥ may be necessary to modulate ␣ 2 ␤ 1 to allow it to bind to collagen.…”

Section: Figmentioning

confidence: 99%

Aggretin, a Heterodimeric C-type Lectin from Calloselasma rhodostoma (Malayan Pit Viper), Stimulates Platelets by Binding to α2β1 Integrin and Glycoprotein Ib, Activating Syk and Phospholipase Cγ2, but Does Not Involve the Glycoprotein VI/Fc Receptor γ Chain Collagen Receptor

Navdaev

Clemetson

Polgár

et al. 2001

Journal of Biological Chemistry

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Aggretin, a potent platelet activator, was isolated from Calloselasma rhodostoma venom, and 30-amino acid N-terminal sequences of both subunits were determined. Aggretin belongs to the heterodimeric snake Ctype lectin family and is thought to activate platelets by binding to platelet glycoprotein ␣ 2 ␤ 1 . We now show that binding to glycoprotein (GP) Ib is also required. Aggretin-induced platelet activation was inhibited by a monoclonal antibody to GPIb as well as by antibodies to ␣ 2 ␤ 1 . Binding of both of these platelet receptors to aggretin was confirmed by affinity chromatography. No binding of other major platelet membrane glycoproteins, in particular GPVI, to aggretin was detected. Aggretin also activates platelets from Fc receptor ␥ chain (Fc␥)-deficient mice to a greater extent than those from normal control mice, showing that it does not use the GPVI/Fc␥ pathway. Platelets from Fc␥-deficient mice expressed fibrinogen receptors normally in response to collagen, although they did not aggregate, indicating that these platelets may partly compensate via other receptors including ␣ 2 ␤ 1 or GPIb for the lack of the Fc␥ pathway. Signaling by aggretin involves a dose-dependent lag phase followed by rapid tyrosine phosphorylation of a number of proteins. Among these are p72 SYK , p125 FAK , and PLC␥2, whereas, in comparison with collagen and convulxin, the Fc␥ subunit neither is phosphorylated nor coprecipitates with p72 SYK . This supports an independent, GPIb-and integrin-based pathway for activation of p72 SYK not involving the Fc␥ receptor.Platelet-collagen interactions are integral to primary hemostasis (1, 2). Resting platelets using several receptors adhering to subendothelium of damaged blood vessels are activated and spread to provide finally a new nonthrombogenic surface until vasculature regeneration occurs. Reversible binding between GPIb-V-IX 1 and von Willebrand factor, associated with collagen, is crucial to slow down the platelet (especially under high shear) so that it can bind more firmly via other receptors (3, 4). This mechanism strongly parallels that of the selectins in leukocyte adhesion (5). Another important receptor is the ␣ 2 ␤ 1 integrin, which is essential for anchoring the platelet to collagen in the subendothelium (6) and for linking to the platelet cytoskeleton to prevent the receptor being torn from the membrane by the forces that it has to withstand. Activation induces the release of storage granules and the expression of new receptors on the platelet surface (7) as well as changes in other receptors such as the fibrinogen receptor, ␣ IIb ␤ 3 , which is critical for spreading. Although GPIb-V-IX and ␣ 2 ␤ 1 also participate in signaling to the platelet interior (8, 9), recent studies, particularly in patients with platelet receptor deficiencies, have implicated GPVI/Fc␥ as a major collagen receptor for platelet activation (10 -12). Patients with platelets lacking any one of these receptors (GPIb-V-IX, ␣ 2 ␤ 1 , or GPVI/Fc␥) have increased bleeding times, and platelet adhesio...

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