Platelet-Dense Granules Worsen Pre-Infection Thrombocytopenia during Gram-Negative Pneumonia-Derived Sepsis

Platelet-dense ( δ) granules are important for platelet function. Platelets contribute to host defense and vascular integrity during pneumonia and sepsis, and δ granule products, including adenosine diphosphate (ADP), can influence inflammatory responses. We therefore aimed to study the role of platelet δ granule s in the host response during sepsis. Hermansky-Pudlak syndrome(Hps)3coa mice (with reduced δ granule content), mice treated with the platelet ADP receptor inhibitor clopidogrel, and appropriate control mice were infected with the human sepsis pathogenKlebsiella pneumoniae via the airways to induce pneumonia and sepsis. In order to override potential redundancy in platelet functions, we also studiedHps3coa and control mice with moderate antibody-induced thrombocytopenia (10%) prior to infection. We found that sepsis-induced thrombocytopenia tended to be less severe inHps3coa mice, and was significantly ameliorated inHps3coa mice with low pre-infection platelet counts. Bacterial growth was similar inHps3coa and control mice in the presence of normal platelet counts prior to infection, but lower in the lungs ofHps3coa mice with low pre-infection platelet counts.Hps3coa mice had unaltered lung pathology and distant organ injury during pneumosepsis, irrespective of pre-infection platelet counts; lung bleeding did not differ betweenHps3coa and control mice. Clopidogrel did not influence any host response parameter. These data suggest that platelet δ granules can play...
Source: Journal of Innate Immunity - Category: Allergy & Immunology Source Type: research