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  - Elgheznawy, Amro
A1  - Öftering, Patricia
A1  - Englert, Maximilian
A1  - Mott, Kristina
A1  - Kaiser, Friederike
A1  - Kusch, Charly
A1  - Gbureck, Uwe
A1  - Bösl, Michael R.
A1  - Schulze, Harald
A1  - Nieswandt, Bernhard
A1  - Vögtle, Timo
A1  - Hermanns, Heike M.
T1  - Loss of zinc transporters ZIP1 and ZIP3 augments platelet reactivity in response to thrombin and accelerates thrombus formation in vivo
JF  - Frontiers in Immunology
N2  - Zinc (Zn2+) is considered as important mediator of immune cell function, thrombosis and haemostasis. However, our understanding of the transport mechanisms that regulate Zn2+ homeostasis in platelets is limited. Zn2+ transporters, ZIPs and ZnTs, are widely expressed in eukaryotic cells. Using mice globally lacking ZIP1 and ZIP3 (ZIP1/3 DKO), our aim was to explore the potential role of these Zn2+ transporters in maintaining platelet Zn2+ homeostasis and in the regulation of platelet function. While ICP-MS measurements indicated unaltered overall Zn2+ concentrations in platelets of ZIP1/3 DKO mice, we observed a significantly increased content of FluoZin3-stainable free Zn2+, which, however, appears to be released less efficiently upon thrombin-stimulated platelet activation. On the functional level, ZIP1/3 DKO platelets exhibited a hyperactive response towards threshold concentrations of G protein-coupled receptor (GPCR) agonists, while immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptor agonist signalling was unaffected. This resulted in enhanced platelet aggregation towards thrombin, bigger thrombus volume under flow ex vivo and faster in vivo thrombus formation in ZIP1/3 DKO mice. Molecularly, augmented GPCR responses were accompanied by enhanced Ca2+ and PKC, CamKII and ERK1/2 signalling. The current study thereby identifies ZIP1 and ZIP3 as important regulators for the maintenance of platelet Zn2+ homeostasis and function.
KW  - platelets
KW  - zinc
KW  - ZIP
KW  - thrombin
KW  - signaling
KW  - thrombosis
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320154
VL  - 14
ER  -