@article{NiklausKlinglerWeberetal.2022,
  author    = {Niklaus, Marius and Klingler, Philipp and Weber, Katja and Koessler, Angela and Kuhn, Sabine and Boeck, Markus and Kobsar, Anna and Koessler, Juergen},
  title     = {Platelet Toll-Like-Receptor-2 and -4 Mediate Different Immune-Related Responses to Bacterial Ligands},
  series = {TH Open},
  volume    = {6},
  journal   = {TH Open},
  number    = {3},
  doi       = {10.1055/a-1827-7365},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301401},
  pages     = {e156 -- e167},
  year      = {2022},
  abstract  = {Background  Like immune cells, platelets express toll-like receptors (TLRs) on their surface membrane. TLR2 and TLR4 are able to recognize bacterial antigens and have the potential to influence hemostatic functions and classical intracellular signaling pathways. This study investigated the role of TLR2 and TLR4 for immune-related functions in human platelets. Materials and Methods  Washed platelets and neutrophils were prepared from fresh human peripheral blood. Basal-, Pam3CSK4- (as TLR2 agonist) and Lipopolysaccharides (LPS; as TLR4 agonist) -induced CD62P expression, fibrinogen binding and TLR2 or TLR4 expression, intracellular reactive oxygen species (ROS) production in H2DCFDA-loaded platelets and uptake of fluorescence-labeled TLR ligands, and fluorophore-conjugated fibrinogen were evaluated by flow cytometry. Analysis of platelet-neutrophil complexes was performed after coincubation of washed platelets and neutrophils in the presence and absence of TLR2 or TLR4 agonists on poly-L-lysine coated surfaces, followed by immunostaining and immunofluorescence imaging. Results  Pam3CSK4 rapidly and transiently increased TLR2 and TLR4 expression. Over the course of 30 minutes after activation with Pam3CSK4 and LPS, the expression of both receptors decreased. Pam3CSK4-stimulated intracellular ROS production and the uptake of TLR ligands or fibrinogen much stronger than LPS. Besides, TLR4 activation led to a significant increase of platelet-neutrophil contacts. Conclusion  Stimulation leads to rapid mobilization of TLR2 or TLR4 to the platelet surface, presumably followed by receptor internalization along with bound TLR ligands. After activation, platelet TLR2 and TLR4 mediate different immune-related reactions. In particular, TLR2 induces intracellular responses in platelets, whereas TLR4 initiates interactions with other immune cells such as neutrophils.},
  language  = {en}
}
@article{KobsarKoehnlechnerKlingleretal.2022,
  author    = {Kobsar, Anna and Koehnlechner, Karina and Klingler, Philipp and Niklaus, Marius and Zeller-Hahn, Julia and Koessler, Angela and Weber, Katja and Boeck, Markus and Koessler, Juergen},
  title     = {The effect of short-term refrigeration on platelet responsiveness},
  series = {Scientific Reports},
  volume    = {12},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-022-21124-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301390},
  year      = {2022},
  abstract  = {Storage of platelet concentrates (PC) at cold temperature (CT) is discussed as an alternative to the current standard of storage at room temperature (RT). Recently, we could show that cold-induced attenuation of inhibitory signaling is an important mechanism promoting platelet reactivity. For developing strategies in blood banking, it is required to elucidate the time-dependent onset of facilitated platelet activation. Thus, freshly prepared platelet-rich-plasma (PRP) was stored for 1 and 2 h at CT (2-6 °C) or at RT (20-24 °C), followed by subsequent comparative analysis. Compared to RT, basal and induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation levels were decreased under CT within 1 h by approximately 20\%, determined by Western blot analysis and flow cytometry. Concomitantly, ADP- and collagen-induced threshold aggregation values were enhanced by up to 30-40\%. Furthermore, platelet-covered areas on collagen-coated slides and aggregate formation under flow conditions were increased after storage at CT, in addition to induced activation markers. In conclusion, a time period of 1-2 h for refrigeration is sufficient to induce an attenuation of inhibitory signaling, accompanied with an enhancement of platelet responsiveness. Short-term refrigeration may be considered as a rational approach to obtain PC with higher functional reactivity for the treatment of hemorrhage.},
  language  = {en}
}
@article{SchosseeVeitGitteletal.2022,
  author    = {Schossee, Nadine and Veit, Gabriele and Gittel, Julia and Viebahn, Johannes and Niklaus, Marius and Klingler, Philipp and {\"U}{\c{c}}eyler, Nurcan and Klinker, Erdwine and Kobsar, Anna and Boeck, Markus and Koessler, Juergen},
  title     = {Profile of the single-use, multiple-pass protein A adsorber column in immunoadsorption},
  series = {Vox Sanguinis},
  volume    = {117},
  journal   = {Vox Sanguinis},
  number    = {3},
  doi       = {10.1111/vox.13205},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259689},
  pages     = {393-398},
  year      = {2022},
  abstract  = {Background and Objectives Immunoadsorptions (IA) are used to remove autoantibodies from the plasma in autoimmune disorders. In this study, we evaluated the effects of a single-use, recombinant staphylococcal protein A-based immunoadsorber on blood composition of the patient. Materials and Methods In a cohort of patients with myasthenia gravis or stiff-person syndrome, essential parameters of blood cell count, coagulation, clinical chemistry or plasma proteins and immunoglobulins (Ig) were measured before and after IA (n = 11). Results In average, IA reduced the levels of total IgG, IgG1, IgG2 and IgG4 by approximately 60\%, the acetylcholine receptor autoantibody levels by more than 70\%. IgG3, IgA or IgM were diminished to a lower extent. In contrast to fibrinogen or other coagulation factors, the column markedly removed vitamin K-dependent coagulation factors II, VII, IX and X by approximately 40\%-70\%. Accordingly, international normalized ratio and activated partial thromboplastin time were increased after IA by 59.1\% and 32.7\%, respectively. Coagulation tests almost returned to baseline values within 24 h. Blood cell count, electrolytes, total protein or albumin were not essentially affected. No clinical events occurred. Conclusion The single-use, multiple-pass protein A adsorber column is highly efficient to remove IgG1, IgG2 and IgG4 or specific acetylcholine receptor autoantibodies from the plasma. Coagulation parameters should be monitored, since the column has the capacity to largely reduce vitamin K-dependent factors.},
  language  = {en}
}