Beyond their role in hemostasis and thrombosis, platelets are also important mediators of inflammation by the release of hundreds of factors stored in their α‐granules. Mutations in Nbeal2 cause gray platelet syndrome (GPS), characterized by the lack of platelet α‐granules. This study aims to evaluate the immunological (proinflammatory) effects of platelet α‐granules.
STUDY DESIGN AND METHODS
We performed an experiment using Nbeal2−/− mice, the mouse model of GPS. Systemic inflammation was induced by intravenous injection of lipopolysaccharide (LPS). Inflammatory response was assessed by quantification of inflammatory soluble factors and platelet biological response modifiers.
The lack of Nbeal2 (in Nbeal2 −/− mice, compared with controls) significantly reduced the recruitment of circulating neutrophils and monocytes. Moreover, after LPS injection, there was a significant increase in neutrophil and monocyte counts in control animals, compared with Nbeal2 −/− mice. The control of inflammation, evaluated by the production of anti‐inflammatory cytokines, appeared to be greater in Nbeal2−/− mice compared with controls. Conversely, the production of certain inflammatory‐soluble mediators known to characterize normal platelet secretion, such as soluble CD40 ligand (sCD40L), was decreased under experimental inflammation in Nbeal2 −/− mice.
These results show that α‐granules play a direct role in platelet‐mediated inflammation balance, confirming the need to further investigate platelet‐associated inflammatory pathophysiology and inflammatory adverse events related to blood transfusion.