Ser/Thr protein kinase Bβ-NADPH oxidase 2 signaling in thromboinflammation.

PURPOSE OF REVIEW

Interactions between neutrophils and platelets contribute to the progression of thromboinflammatory disease. However, the regulatory mechanism governing these interactions is poorly understood. The present review focuses on the crucial role of Ser/Thr protein kinase B (AKT)β-NADPH oxidase 2 (NOX2) signaling in regulating neutrophil and platelet activation and their heterotypic interactions under thromboinflammatory conditions.

RECENT FINDINGS

Growing evidence has shown that platelets, leukocytes, and blood coagulation need to be considered to treat thromboinflammatory disease in which inflammation and thrombosis occur concurrently. In addition to plasma proteins and intracellular signaling molecules, extracellular reactive oxygen species (ROS) produced from activated leukocytes could be an important factor in the pathophysiology of thromboinflammatory disease. Recent studies reveal that AKT2-NOX2 signaling has critical roles in Ca mobilization, ROS generation, degranulation, and control of the ligand-binding function of cell surface molecules, thereby promoting heterotypic cell-cell interactions in thromboinflammation. These findings have provided novel insights into attractive therapeutic targets for the prevention and treatment of thromboinflammatory disease.

SUMMARY

Recent discoveries concerning molecular mechanisms regulating neutrophil-platelet interactions have bridged some gaps in our knowledge of the complicated signaling pathways exacerbating thromboinflammatory conditions.