Pathological interactions between blood cells promote thrombo-inflammatory disease and result in complications such as vaso-occlusion during atherothrombosis, inflammation, and ischemia. Activated platelets, leukocytes and endothelial cells all contribute to the development of vaso-occlusion: though how interactions between these cell types are regulated is poorly understood.
In this issue of the Journal of Clinical Investigation, Jaehyung Cho and colleagues at the University of Illinois determined that the serine/threonine kinase AKT2 was required for heterotypic aggregation of activated platelets, neutrophils and endothelial cells during TNF-α-induced vascular inflammation.
In neutrophils, AKT2 phosphorylation activated and resulted in membrane translocation of αMβ2 integrin, which promoted cell-cell attachment. Neutrophils and platelets from patients with sickle cell disease (SCD) had increased levels of AKT phosphorylation, and specific inhibition of AKT2 diminished aggregation of these patients' cells. In SCD mice, targeting AKT2 reduced platelet-neutrophil aggregation and improved blood flow rates. In a companion Commentary, Gregory Vercellotti and John Belcher of the University of Minnesota discuss the complicated etiology of SCD-associated vaso-occlusion.