TY  - JOUR
A1  - Chen, Chunguang
A1  - Rawat, Divya
A1  - Samikannu, Balaji
A1  - Bender, Markus
A1  - Preissner, Klaus T.
A1  - Linn, Thomas
T1  - Platelet glycoprotein VI‐dependent thrombus stabilization is essential for the intraportal engraftment of pancreatic islets
JF  - American Journal of Transplantation
N2  - Platelet activation and thrombus formation have been implicated to be detrimental for intraportal pancreatic islet transplants. The platelet‐specific collagen receptor glycoprotein VI (GPVI) plays a key role in thrombosis through cellular activation and the subsequent release of secondary mediators. In aggregometry and in a microfluidic dynamic assay system modeling flow in the portal vein, pancreatic islets promoted platelet aggregation and triggered thrombus formation, respectively. While platelet GPVI deficiency did not affect the initiation of these events, it was found to destabilize platelet aggregates and thrombi in this process. Interestingly, while no major difference was detected in early thrombus formation after intraportal islet transplantation, genetic GPVI deficiency or acute anti‐GPVI treatment led to an inferior graft survival and function in both syngeneic mouse islet transplantation and xenogeneic human islet transplantation models. These results demonstrate that platelet GPVI signaling is indispensable in stable thrombus formation induced by pancreatic islets. GPVI deficiency resulted in thrombus destabilization and inferior islet engraftment indicating that thrombus formation is necessary for a successful intraportal islet transplantation in which platelets are active modulators.
KW  - basic (laboratory) research / science
KW  - coagulation and hemostasis
KW  - graft survival
KW  - islet transplantation
KW  - molecular biology
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224471
VL  - 21
SP  - 2079
EP  - 2089
ER  - 
TY  - JOUR
A1  - Chillo, Omary
A1  - Kleinert, Eike Christian
A1  - Lautz, Thomas
A1  - Lasch, Manuel
A1  - Pagel, Judith-Irina
A1  - Heun, Yvonn
A1  - Troidl, Kerstin
A1  - Fischer, Silvia
A1  - Caballero-Martinez, Amelia
A1  - Mauer, Annika
A1  - Kurz, Angela R. M.
A1  - Assmann, Gerald
A1  - Rehberg, Markus
A1  - Kanse, Sandip M.
A1  - Nieswandt, Bernhard
A1  - Walzog, Barbara
A1  - Reichel, Christoph A.
A1  - Mannell, Hanna
A1  - Preissner, Klaus T.
A1  - Deindl, Elisabeth
T1  - Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function
JF  - Cell Reports
N2  - The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit+/CXCR-4+ cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases.
KW  - Mast cells
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164800
VL  - 16
IS  - 8
ER  -