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Pathogenic interactions between platelets and neutrophils are mediated by AKT2

Pathological interactions between blood cells promote thrombo-inflammatory disease and result in complications such as vaso-occlusion during atherothrombosis, inflammation, and ischemia. Activated , leukocytes and 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 , Jaehyung Cho and colleagues at the University of Illinois determined that the serine/threonine kinase AKT2 was required for heterotypic aggregation of activated platelets, and endothelial cells during TNF-?-induced .

In neutrophils, AKT2 phosphorylation activated and resulted in membrane translocation of ?M?2 integrin, which promoted cell-cell attachment. Neutrophils and platelets from patients with (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.


Neutrophil AKT2 regulates heterotypic cell-cell interactions during vascular inflammation

Accompanying commentary:

Not simply misshapen red cells: multimolecular and cellular events in sickle vaso-occlusion


JCI online ahead of print, March 18, 2014

Journal of Clinical Investigation