TY  - JOUR
A1  - Popp, Michael
A1  - Thielman, Ina
A1  - Nieswandt, Bernhard
A1  - Stegner, David
T1  - Normal Platelet Integrin Function in Mice Lacking Hydrogen Peroxide-Induced Clone-5 (Hic-5)
JF  - PLoS One
N2  - Integrin αIIbβ3 plays a central role in the adhesion and aggregation of platelets and thus is essential for hemostasis and thrombosis. Integrin activation requires the transmission of a signal from the small cytoplasmic tails of the α or β subunit to the large extracellular domains resulting in conformational changes of the extracellular domains to enable ligand binding. Hydrogen peroxide-inducible clone-5 (Hic-5), a member of the paxillin family, serves as a focal adhesion adaptor protein associated with αIIbβ3 at its cytoplasmic tails. Previous studies suggested Hic-5 as a novel regulator of integrin αIIbβ3 activation and platelet aggregation in mice. To assess this in more detail, we generated Hic-5-null mice and analyzed activation and aggregation of their platelets in vitro and in vivo. Surprisingly, lack of Hic-5 had no detectable effect on platelet integrin activation and function in vitro and in vivo under all tested conditions. These results indicate that Hic-5 is dispensable for integrin αIIbβ3 activation and consequently for arterial thrombosis and hemostasis in mice.
KW  - platelet activation
KW  - fibrinogen
KW  - integrins
KW  - platelets
KW  - thrombin
KW  - flow cytometry
KW  - platelet aggregation
KW  - blood
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125724
VL  - 10
IS  - 7
ER  - 
TY  - JOUR
A1  - Hofmann, Sebastian
A1  - Braun, Attila
A1  - Pozgaj, Rastislav
A1  - Morowski, Martina
A1  - Vögtle, Timo
A1  - Nieswandt, Bernhard
T1  - Mice lacking the SLAM family member CD84 display unaltered platelet function in hemostasis and thrombosis
JF  - PLoS One
N2  - Background
Platelets are anuclear cell fragments derived from bone marrow megakaryocytes that safeguard vascular integrity by forming thrombi at sites of vascular injury. Although the early events of thrombus formation—platelet adhesion and aggregation—have been intensively studied, less is known about the mechanisms and receptors that stabilize platelet-platelet interactions once a thrombus has formed. One receptor that has been implicated in this process is the signaling lymphocyte activation molecule (SLAM) family member CD84, which can undergo homophilic interactions and becomes phosphorylated upon platelet aggregation.

Objective
The role of CD84 in platelet physiology and thrombus formation was investigated in CD84-deficient mice.

Methods and Results
We generated CD84-deficient mice and analyzed their platelets in vitro and in vivo. \(Cd84^{−/−}\) platelets exhibited normal activation and aggregation responses to classical platelet agonists. Furthermore, CD84 deficiency did not affect integrin-mediated clot retraction and spreading of activated platelets on fibrinogen. Notably, also the formation of stable three-dimensional thrombi on collagen-coated surfaces under flow ex vivo was unaltered in the blood of \(Cd84^{−/−}\) mice. In vivo, \(Cd84^{−/−}\) mice exhibited unaltered hemostatic function and arterial thrombus 
formation.

Conclusion
These results show that CD84 is dispensable for thrombus formation and stabilization, indicating that its deficiency may be functionally compensated by other receptors or that it may be important for platelet functions different from platelet-platelet interactions.
KW  - flow cytometry
KW  - CD coreceptors
KW  - integrins
KW  - blood
KW  - platelet aggregation
KW  - platelet activation
KW  - cytotoxic T cells
KW  - platelets
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126477
VL  - 9
IS  - 12
ER  -