Lung innate immune activation results in acute lung inflammation, which is characterized by alveolar barrier disruption and accumulation of cellular lung aggregates comprising neutrophils, platelets, mononuclear cells, and microparticles. CD34 is a sialomucin, with pan-selectin affinity and recently shown to protect the endothelial barrier in a bleomycin-induced lung injury model. However, there is very little information about the fundamental role of CD34 in regulation of the lung innate immune response. We hypothesized that CD34 regulates leukocyte recruitment by promoting optimal platelet activation (aggregation and spread) during bacterial lipopolysaccharide (LPS)-induced acute lung injury. Therefore, we utilized CD34 knock-out (KO) and wild-type (WT) mice to analyze and compare the morphology and expression of leukocyte subsets from the pulmonary and systemic compartments. We utilized the chemotactic N-formylated tri-peptide, fMLP, to understand platelet aggregation in vitro, and the fundamental immune stimulant, LPS, to induce lung injury and understand platelet activation ex vivo. Our data reveal that under steady-state conditions, KO mice possess large aggregates of integrin β3 (CD61)-positive microparticles in peripheral blood. Moreover, the KO mice recruit a large number of neutrophils to lungs, which are not cleared even at 36-h post-LPS exposure. The KO mice display an increased platelet CD61 expression, which aggregates, but does not spread normally in response to in vitro fMLP treatment. The KO platelets display similar deficits in their spreading ability even after ex vivo LPS exposure. Thus, our data demonstrate that CD34 modulates platelet biology, microparticle aggregation, and neutrophil recruitment during murine lung inflammation.

中文翻译：

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CD34 缺乏会导致血小板、微粒和肺部炎症缺陷

肺先天免疫激活导致急性肺部炎症，其特征是肺泡屏障破坏和肺细胞聚集体的积聚，包括中性粒细胞、血小板、单核细胞和微粒。CD34 是一种唾液粘蛋白​​，具有泛选择素亲和力，最近在博莱霉素诱导的肺损伤模型中显示出保护内皮屏障。然而，关于 CD34 在调节肺先天免疫反应中的基本作用的信息很少。我们假设 CD34 通过在细菌脂多糖 (LPS) 诱导的急性肺损伤期间促进最佳血小板活化（聚集和扩散）来调节白细胞募集。所以，我们利用 CD34 敲除 (KO) 和野生型 (WT) 小鼠来分析和比较来自肺和全身区室的白细胞亚群的形态和表达。我们利用趋化性 N-甲酰化三肽 fMLP 来了解体外血小板聚集，并利用基本免疫刺激剂 LPS 来诱导肺损伤并了解体外血小板活化。我们的数据显示，在稳态条件下，KO 小鼠在外周血中具有大量整合素 β3 (CD61) 阳性微粒。此外，KO 小鼠将大量中性粒细胞募集到肺部，即使在 LPS 暴露后 36 小时，这些中性粒细胞也不会被清除。KO 小鼠表现出增加的血小板 CD61 表达，该表达会聚集，但不会响应体外 fMLP 治疗而正常扩散。即使在离体 LPS 暴露后，KO 血小板在其扩散能力方面也表现出类似的缺陷。因此，我们的数据表明 CD34 在小鼠肺部炎症期间调节血小板生物学、微粒聚集和中性粒细胞募集。