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 (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 pathogen Klebsiella pneumoniae via the airways to induce pneumonia and sepsis. In order to override potential redundancy in platelet functions, we also studied Hps3coa and control mice with moderate antibody-induced thrombocytopenia (10%) prior to infection. We found that sepsis-induced thrombocytopenia tended to be less severe in Hps3coa mice, and was significantly ameliorated in Hps3coa mice with low pre-infection platelet counts. Bacterial growth was similar in Hps3coa and control mice in the presence of normal platelet counts prior to infection, but lower in the lungs of Hps3coa 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 between Hps3coa 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.

中文翻译：

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革兰氏阴性肺炎衍生败血症期间，血小板致密颗粒易感染前血小板减少症。

血小板致密（δ）颗粒对于血小板功能很重要。血小板在肺炎和败血症期间有助于宿主防御和血管完整性，并且包括二磷酸腺苷（ADP）在内的δ颗粒产品可影响炎症反应。因此，我们旨在研究败血症过程中血小板δ颗粒在宿主反应中的作用。Hermansky-Pudlak综合征（Hps）3coa小鼠（δ颗粒含量降低），用血小板ADP受体抑制剂氯吡格雷治疗的小鼠以及适当的对照小鼠经呼吸道感染了人类败血症病原体肺炎克雷伯菌，从而诱发肺炎和败血症。为了消除血小板功能的潜在冗余，我们还研究了Hps3coa和具有感染前中度抗体诱导的血小板减少症（10％）的对照小鼠。我们发现败血症诱导的血小板减少症在Hps3coa小鼠中趋向于不严重，而在感染前血小板计数低的Hps3coa小鼠中则得到明显改善。在感染前存在正常血小板计数的情况下，Hps3coa和对照小鼠的细菌生长相似，但感染前血小板计数低的Hps3coa小鼠的细菌生长较慢。Hps3coa小鼠在肺炎发作期间具有不变的肺部病理学特征和远处器官损伤，与感染前血小板计数无关。Hps3coa和对照小鼠之间的肺出血没有差异。氯吡格雷不影响任何宿主反应参数。这些数据表明，血小板δ颗粒可通过加重血小板减少症和削弱局部抗菌防御作用而在肺炎中起有害作用，