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  - 
TY  - JOUR
A1  - Nieswandt, Bernhard
A1  - Morowski, Martina
A1  - Brachs, Sebastian
A1  - Mielenz, Dirk
A1  - Dütting, Sebastian
T1  - The Adaptor Protein Swiprosin-1/EFhd2 Is Dispensable for Platelet Function in Mice
N2  - Background

Platelets are anuclear cell fragments derived from bone marrow megakaryocytes that safeguard vascular integrity, but may also cause pathological vessel occlusion. Reorganizations of the platelet cytoskeleton and agonist-induced intracellular Ca2+-mobilization are crucial for platelet hemostatic function. EF-hand domain containing 2 (EFhd2, Swiprosin-1) is a Ca2+-binding cytoskeletal adaptor protein involved in actin remodeling in different cell types, but its function in platelets is unknown.

Objective

Based on the described functions of EFhd2 in immune cells, we tested the hypothesis that EFhd2 is a crucial adaptor protein for platelet function acting as a regulator of Ca2+-mobilization and cytoskeletal rearrangements.

Methods and Results

We generated EFhd2-deficient mice and analyzed their platelets in vitro and in vivo. Efhd2-/- mice displayed normal platelet count and size, exhibited an unaltered in vivo life span and showed normal Ca2+-mobilization and activation/aggregation responses to classic agonists. Interestingly, upon stimulation of the immunoreceptor tyrosine-based activation motif-coupled receptor glycoprotein (GP) VI, Efhd2-/- platelets showed a slightly increased coagulant activity. Furthermore, absence of EFhd2 had no significant impact on integrin-mediated clot retraction, actomyosin rearrangements and spreading of activated platelets on fibrinogen. In vivo EFhd2-deficiency resulted in unaltered hemostatic function and unaffected arterial thrombus formation.

Conclusion

These results show that EFhd2 is not essential for platelet function in mice indicating that other cytoskeletal adaptors may functionally compensate its loss.
KW  - adaptor protein Swiprosin-1/EFhd2
KW  - platelets
KW  - platelet activation
KW  - platelet aggregation
KW  - cytoskeleton
KW  - thrombin
KW  - blood
KW  - actins
KW  - collagens
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-113316
ER  -