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A role for adhesion and degranulation‐promoting adapter protein in collagen‐induced platelet activation mediated via integrin α2β1
- Source :
- Journal of Thrombosis and Haemostasis. 10:268-277
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
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 α2β1. Adhesion and degranulation-promoting adapter protein (ADAP) regulates αIIbβ3 in platelets and αLβ2 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 α2β1. 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 α2β1-selective ligand GFOGER and to a peptide (III-04), which supports adhesion that is dependent on both GPVI and α2β1, 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 α2β1. 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.
- Subjects :
- Blood Platelets
CD36 Antigens
Time Factors
Platelet Aggregation
Integrin
Immunoglobulin Variable Region
Platelet Glycoprotein GPIIb-IIIa Complex
Article
Mice
Thromboxane A2
chemistry.chemical_compound
Platelet Adhesiveness
Platelet adhesiveness
Animals
Platelet
Pseudopodia
Platelet activation
Phosphorylation
Adaptor Proteins, Signal Transducing
Mice, Knockout
biology
Phospholipase C gamma
Tyrosine phosphorylation
Hematology
Platelet Activation
Thrombocytopenia
Cell biology
Mice, Inbred C57BL
Thromboxane B2
chemistry
Biochemistry
Splenomegaly
biology.protein
Tyrosine
Collagen
Integrin alpha2beta1
GPVI
Carrier Proteins
Peptides
Subjects
Details
- ISSN :
- 15387836
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of Thrombosis and Haemostasis
- Accession number :
- edsair.doi.dedup.....c80f0730f085f386f86675f2612f849a