A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) β(1).

Research output: Contribution to journalArticle

Standard

A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) β(1). / Jarvis, GE; Bihan, D; Hamaia, S; Pugh, N; Ghevaert, CJ; Pearce, AC; Hughes, Craig; Watson, SP; Ware, J; Rudd, CE; Farndale, RW.

In: Journal of Thrombosis and Haemostasis, Vol. 10, No. 2, 01.02.2012, p. 268-77.

Research output: Contribution to journalArticle

Harvard

APA

Vancouver

Author

Jarvis, GE ; Bihan, D ; Hamaia, S ; Pugh, N ; Ghevaert, CJ ; Pearce, AC ; Hughes, Craig ; Watson, SP ; Ware, J ; Rudd, CE ; Farndale, RW. / A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) β(1). In: Journal of Thrombosis and Haemostasis. 2012 ; Vol. 10, No. 2. pp. 268-77.

Bibtex

@article{446f64c475a0489182b3bacf0db9ed01,
title = "A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) β(1).",
abstract = "Summary.  Background: Collagen-induced platelet activation is a key step in the development of arterial thrombosis via its interaction with the receptors glycoprotein (GP)VI and integrin α(2) β(1) . Adhesion and degranulation-promoting adapter protein (ADAP) regulates α(IIb) β(3) in platelets and α(L) β(2) in T cells, and is phosphorylated in GPVI-deficient platelets activated by collagen. Objectives: To determine whether ADAP plays a role in collagen-induced platelet activation and in the regulation and function of α(2) β(1) . Methods: Using ADAP(-/-) mice and synthetic collagen peptides, we investigated the role of ADAP in platelet aggregation, adhesion, spreading, thromboxane synthesis, and tyrosine phosphorylation. Results and Conclusions: Platelet aggregation and phosphorylation of phospholipase Cγ2 induced by collagen were attenuated in ADAP(-/-) platelets. However, aggregation and signaling induced by collagen-related peptide (CRP), a GPVI-selective agonist, were largely unaffected. Platelet adhesion to CRP was also unaffected by ADAP deficiency. Adhesion to the α(2) β(1) -selective ligand GFOGER and to a peptide (III-04), which supports adhesion that is dependent on both GPVI and α(2) β(1) , was reduced in ADAP(-/-) platelets. An impedance-based label-free detection technique, which measures adhesion and spreading of platelets, indicated that, in the absence of ADAP, spreading on GFOGER was also reduced. This was confirmed with non-fluorescent differential-interference contrast microscopy, which revealed reduced filpodia formation in ADAP(-/-) platelets adherent to GFOGER. This indicates that ADAP plays a role in mediating platelet activation via the collagen-binding integrin α(2) β(1) . In addition, we found that ADAP(-/-) mice, which are mildly thrombocytopenic, have enlarged spleens as compared with wild-type animals. This may reflect increased removal of platelets from the circulation.",
author = "GE Jarvis and D Bihan and S Hamaia and N Pugh and CJ Ghevaert and AC Pearce and Craig Hughes and SP Watson and J Ware and CE Rudd and RW Farndale",
year = "2012",
month = feb,
day = "1",
doi = "10.1111/j.1538-7836.2011.04567.x",
language = "English",
volume = "10",
pages = "268--77",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley",
number = "2",

}

RIS

TY - JOUR

T1 - A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) β(1).

AU - Jarvis, GE

AU - Bihan, D

AU - Hamaia, S

AU - Pugh, N

AU - Ghevaert, CJ

AU - Pearce, AC

AU - Hughes, Craig

AU - Watson, SP

AU - Ware, J

AU - Rudd, CE

AU - Farndale, RW

PY - 2012/2/1

Y1 - 2012/2/1

N2 - Summary.  Background: Collagen-induced platelet activation is a key step in the development of arterial thrombosis via its interaction with the receptors glycoprotein (GP)VI and integrin α(2) β(1) . Adhesion and degranulation-promoting adapter protein (ADAP) regulates α(IIb) β(3) in platelets and α(L) β(2) in T cells, and is phosphorylated in GPVI-deficient platelets activated by collagen. Objectives: To determine whether ADAP plays a role in collagen-induced platelet activation and in the regulation and function of α(2) β(1) . Methods: Using ADAP(-/-) mice and synthetic collagen peptides, we investigated the role of ADAP in platelet aggregation, adhesion, spreading, thromboxane synthesis, and tyrosine phosphorylation. Results and Conclusions: Platelet aggregation and phosphorylation of phospholipase Cγ2 induced by collagen were attenuated in ADAP(-/-) platelets. However, aggregation and signaling induced by collagen-related peptide (CRP), a GPVI-selective agonist, were largely unaffected. Platelet adhesion to CRP was also unaffected by ADAP deficiency. Adhesion to the α(2) β(1) -selective ligand GFOGER and to a peptide (III-04), which supports adhesion that is dependent on both GPVI and α(2) β(1) , was reduced in ADAP(-/-) platelets. An impedance-based label-free detection technique, which measures adhesion and spreading of platelets, indicated that, in the absence of ADAP, spreading on GFOGER was also reduced. This was confirmed with non-fluorescent differential-interference contrast microscopy, which revealed reduced filpodia formation in ADAP(-/-) platelets adherent to GFOGER. This indicates that ADAP plays a role in mediating platelet activation via the collagen-binding integrin α(2) β(1) . In addition, we found that ADAP(-/-) mice, which are mildly thrombocytopenic, have enlarged spleens as compared with wild-type animals. This may reflect increased removal of platelets from the circulation.

AB - Summary.  Background: Collagen-induced platelet activation is a key step in the development of arterial thrombosis via its interaction with the receptors glycoprotein (GP)VI and integrin α(2) β(1) . Adhesion and degranulation-promoting adapter protein (ADAP) regulates α(IIb) β(3) in platelets and α(L) β(2) in T cells, and is phosphorylated in GPVI-deficient platelets activated by collagen. Objectives: To determine whether ADAP plays a role in collagen-induced platelet activation and in the regulation and function of α(2) β(1) . Methods: Using ADAP(-/-) mice and synthetic collagen peptides, we investigated the role of ADAP in platelet aggregation, adhesion, spreading, thromboxane synthesis, and tyrosine phosphorylation. Results and Conclusions: Platelet aggregation and phosphorylation of phospholipase Cγ2 induced by collagen were attenuated in ADAP(-/-) platelets. However, aggregation and signaling induced by collagen-related peptide (CRP), a GPVI-selective agonist, were largely unaffected. Platelet adhesion to CRP was also unaffected by ADAP deficiency. Adhesion to the α(2) β(1) -selective ligand GFOGER and to a peptide (III-04), which supports adhesion that is dependent on both GPVI and α(2) β(1) , was reduced in ADAP(-/-) platelets. An impedance-based label-free detection technique, which measures adhesion and spreading of platelets, indicated that, in the absence of ADAP, spreading on GFOGER was also reduced. This was confirmed with non-fluorescent differential-interference contrast microscopy, which revealed reduced filpodia formation in ADAP(-/-) platelets adherent to GFOGER. This indicates that ADAP plays a role in mediating platelet activation via the collagen-binding integrin α(2) β(1) . In addition, we found that ADAP(-/-) mice, which are mildly thrombocytopenic, have enlarged spleens as compared with wild-type animals. This may reflect increased removal of platelets from the circulation.

U2 - 10.1111/j.1538-7836.2011.04567.x

DO - 10.1111/j.1538-7836.2011.04567.x

M3 - Article

C2 - 22103309

VL - 10

SP - 268

EP - 277

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 2

ER -