Complement- and platelet-mediated shuttling of blood-borne bacteria to CD8A+ dendritic cells

Abstract

Beyond its role in innate immunity, complement mediates a ide range of functions in tissue remodeling. Although activaion of platelets is crucial during tissue injury and remodeling n multiple diseases, the exact mechanisms how platelet funcions are modulated by complement components remain elusive. e found that platelets express the complement receptor C3aR. timulation of isolated platelets with C3a peptide enhanced ADP nduced aggregation of platelets using aggregometry and resulted n increased adhesion of platelets to fibrinogen under arterial ow conditions. Moreover, platelets isolated from C3aR−/− mice evealed reduced spreading on fibrinogen. In vivo using C3a recepor knockout mice and C5a receptor knockout mice we could emonstrate that specifically lack of the C3a receptor resulted in educed thrombus formation after vascular injury in an intravial microscopy setting. Accordingly, C3aR-deficient mice displayed ncreased bleeding time in tail bleeding time experiments, which ould not be explained by a difference in peripheral platelet count, nd after reperfusion of C3aR+/+ platelets into C3aR−/− mice proongedbleeding timeassociatedwithC3aRdeficiencywas reversed. n an experimental stroke model, C3aR−/− mice displayed reduced nfarct volume, a difference that was abolished in the absence of latelets. In conclusion, these data indicate a new and surprising unctionof theanaphylatoxin receptorC3aRonplatelets forplatelet unction and thrombosis.