Journal
CELLS
Volume 11, Issue 19, Pages -Publisher
MDPI
DOI: 10.3390/cells11193009
Keywords
platelets; ischemia; ischemic preconditioning; ATP; ADP; adenosine; VASP phosphory-lation; ADORAs; P2Y(12)
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [374031971, NU53/13-1]
Ask authors/readers for more resources
This study investigated the role of extracellular platelet nucleotide signaling in ischemic inflammatory response (IIR) and identified a cybernetic circle, including feedback loops, in the regulation of platelet function in IIR. The study confirmed the presence of different components and feedback loops in the cybernetic system and demonstrated the impact of platelet-neutrophil complex (PNC) formation on blood and inflamed tissue. The integration of extracellular nucleotide signaling, PNC formation, and tissue damage in IIR was described through this study.
Ischemic events are associated with severe inflammation and are here referred to as ischemic inflammatory response (IIR). Recent studies identified the formation of platelet-neutrophil complexes (PNC) as key players in IIR. We investigated the role of extracellular platelet nucleotide signaling in the context of IIR and defined a cybernetic circle, including description of feedback loops. Cybernetic circles seek to integrate different levels of information to understand how biological systems function. Our study specifies the components of the cybernetic system of platelets in IIR and describes the theoretical progression of IIR passing the cybernetic cycle with positive and negative feedback loops based on nucleotide-dependent signaling and functional regulation. The cybernetic components and feedback loops were explored by cytometry, immunohistological staining, functional blocking antibodies, and ADP/ATP measurements. Using several ex vivo and in vivo approaches we confirmed cybernetic parameters, such as controller, sensor, and effector (VASP phosphorylation, P2Y(12), ADORAs and GPIIb/IIIa activity), as well as set points (ADP, adenosine) and interfering control and disturbance variables (ischemia). We demonstrate the impact of the regulated platelet-neutrophil complex (PNC) formation in blood and the resulting damage to the affected inflamed tissue. Taken together, extracellular nucleotide signaling, PNC formation, and tissue damage in IIR can be integrated in a controlled cybernetic circle of platelet function, as introduced through this study.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available