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Complementary roles of platelet glycoprotein VI and integrin α2β1 in collagen‐induced thrombus formation in flowing whole blood ex vivo
Author(s) -
Kuijpers Marijke J. E.,
Schulte Valerie,
Bergmeier Wolfgang,
Lindhout Theo,
Brakebusch Cord,
Offermanns Stefan,
Fässler Reinhard,
Heemskerk Johan W. M.,
Nieswandt Bernhard
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0381fje
Subject(s) - gpvi , platelet , collagen receptor , integrin , chemistry , ex vivo , thrombus , platelet activation , microbiology and biotechnology , vitronectin , thromboxane a2 , platelet membrane glycoprotein , immunology , receptor , biochemistry , medicine , biology , in vitro
Platelets interact vigorously with subendothelial collagens that are exposed by injury or pathological damage of a vessel wall. The collagen‐bound platelets trap other platelets to form aggregates, and they expose phosphatidylserine (PS) required for coagulation. Both processes are implicated in the formation of vaso‐occlusive thrombi. We previously demonstrated that the immunoglobulin receptor glycoprotein VI (GPVI), but not integrin α2β1, is essential in priming platelet‐collagen interaction and subsequent aggregation. Here, we report that these receptors have yet a complementary function in ex vivo thrombus formation during perfusion of whole blood over collagen. With mice deficient in GPVI or blocking antibodies, we found that GPVI was indispensable for collagen‐dependent Ca 2+ mobilization, exposure of PS, and aggregation of platelets. Deficiency of integrin β1 reduces the GPVI‐evoked responses but still allows the formation of loose platelet aggregates. By using mice deficient in Gαq or specific thromboxane A 2 and ADP antagonists, we show that these autocrine agents mediated aggregation but not collagen‐induced Ca 2+ mobilization or PS exposure. Collectively, these data indicate that integrin α2β1 facilitates the central function of GPVI in the platelet activation processes that lead to thrombus formation, whereas the autocrine thromboxane A 2 and ADP serve mainly to trigger aggregate formation.