10.6084/m9.figshare.7472102.v1
Claushuis T.A.M.
Claushuis
T.A.M.
deVos A.F.
deVos
A.F.
Roelofs J.J.T.H.
Roelofs
J.J.T.H.
deBoer O.J.
deBoer
O.J.
van’tVeer C.
van’tVeer
C.
vanderPoll T.
vanderPoll
T.
Supplementary Material for: Platelet-Dense Granules Worsen Pre-Infection Thrombocytopenia during Gram-Negative Pneumonia-Derived Sepsis
Karger Publishers
2018
Animal models
Bacterial infection
Host defense
Platelets
Sepsis
2018-12-17 09:06:39
Dataset
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Platelet-Dense_Granules_Worsen_Pre-Infection_Thrombocytopenia_during_Gram-Negative_Pneumonia-Derived_Sepsis/7472102
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 granules in the host response during sepsis. Hermansky-Pudlak syndrome <i>(Hps)3coa</i> 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 pathogen <i>Klebsiella pneumoniae</i> via the airways to induce pneumonia and sepsis. In order to override potential redundancy in platelet functions, we also studied <i>Hps3coa</i> and control mice with moderate antibody-induced thrombocytopenia (10%) prior to infection. We found that sepsis-induced thrombocytopenia tended to be less severe in <i>Hps3coa</i> mice, and was significantly ameliorated in <i>Hps3coa</i> mice with low pre-infection platelet counts. Bacterial growth was similar in <i>Hps3coa</i> and control mice in the presence of normal platelet counts prior to infection, but lower in the lungs of <i>Hps3coa</i> mice with low pre-infection platelet counts. <i>Hps3coa</i> mice had unaltered lung pathology and distant organ injury during pneumosepsis, irrespective of pre-infection platelet counts; lung bleeding did not differ between <i>Hps3coa</i> and control mice. Clopidogrel did not influence any host response parameter. These data suggest that platelet δ granules can play a detrimental role in pneumosepsis by aggravating thrombocytopenia and impairing local antibacterial defense, but that these unfavorable effects only become apparent in the presence of low platelet counts.