Title:The Role of P2Y12 Receptor and Activated Platelets During Inflammation
Volume: 15
Issue: 7
Author(s): Elisabetta Liverani, Laurie E. Kilpatrick, Alexander Y. Tsygankov and Satya P. Kunapuli
Affiliation:
Keywords:
Inflammation, P2Y12 receptor, platelets and thienopyridines.
Abstract: Platelets play an important role not only during thrombosis, but also in modulating immune responses through
their interaction with immune cells and by releasing inflammatory mediators upon activation. The P2Y12 receptor is a Gicoupled
receptor that not only regulates ADP-induced aggregation but can also dramatically potentiate secretion, when
platelets are activated by other stimuli. Considering the importance of P2Y12 receptor in platelet function, a class of antiplatelet
drugs, thienopyridines, have been designed and successfully used to prevent thrombosis. This review will focus on
the role of activated platelets in inflammation and the effects that P2Y12 antagonism exerts on the inflammatory process. A
change in platelet functions was noted in patients treated with thienopyridines during inflammatory conditions, suggesting
that platelets may modulate the inflammatory response. Further experiments in a variety of animal models of diseases,
such as sepsis, rheumatoid arthritis, myocardial infarction, pancreatitis and pulmonary inflammation have also
demonstrated that activated platelets influence the inflammatory state. Platelets can secrete inflammatory modulators in a
P2Y12–dependent manner, and, as a result, directly alter the inflammatory response. P2Y12 receptor may also be expressed
in other cells of the immune system, indicating that thienopyridines could directly influence the immune system rather
than only through platelets. Overall the results obtained to date strongly support the notion that activated platelets
significantly contribute to the inflammatory process and that antagonizing P2Y12 receptor can influence the immune
response.
