Abstract：
Neutrophils are the first leukocytes to be recruited to sites of inflammation in response to chemotactic factors released by activated macrophages and pulmonary epithelial and endothelial cells in bacterial pneumonia, a common cause of acute respiratory distress syndrome (ARDS). Although neutrophilic inflammation facilitates the elimination of pathogens, neutrophils also may cause bystander tissue injury. Even though neutrophils in alveolar spaces is a key feature of acute lung injury and ARDS especially from pneumonia, their contribution to the pathogenesis of lung injury is uncertain. The goal of this study was to elucidate the role of neutrophils in a clinically relevant model of bacterial pneumonia. We investigated the effect of reducing neutrophils in a mouse model of pneumococcal pneumonia treated with antibiotics. Neutrophils were reduced with anti-Ly6G monoclonal antibody 24 hours before and immediately preceding infection. Mice were inoculated intranasally with Streptococcus pneumoniae and received ceftriaxone 12 hours after bacterial inoculation. Neutrophil reduction in mice treated with ceftriaxone attenuated hypoxemia, alveolar permeability, epithelial injury, pulmonary edema, and inflammatory biomarker release induced by bacterial pneumonia, even though bacterial loads in the distal air spaces of the lung were modestly increased as compared to antibiotic treatment alone. Thus, when appropriate antibiotics are administered, lung injury in the early phase of bacterial pneumonia is mediated in part by neutrophils. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense.
摘要：
中性粒细胞是在细菌性肺炎中响应于活化的巨噬细胞和肺上皮细胞和内皮细胞释放的趋化因子而募集到炎症部位的第一个白细胞，急性呼吸窘迫综合征（ARDS）的常见原因。虽然嗜中性炎症有助于消除病原体，中性粒细胞也可能导致旁观者组织损伤。尽管肺泡间隙中的中性粒细胞是急性肺损伤和ARDS的关键特征，尤其是肺炎，它们对肺损伤的发病机制的贡献尚不确定。这项研究的目的是阐明中性粒细胞在细菌性肺炎临床相关模型中的作用。我们研究了用抗生素治疗的肺炎球菌肺炎小鼠模型中减少中性粒细胞的作用。在感染前24小时和感染前立即用抗Ly6G单克隆抗体减少嗜中性粒细胞。用肺炎链球菌鼻内接种小鼠,并在细菌接种后12小时接受头孢曲松。头孢曲松治疗小鼠的中性粒细胞减少，肺泡通透性，上皮损伤，肺水肿,和细菌性肺炎引起的炎症生物标志物释放，尽管与单纯抗生素治疗相比,肺远端空气间隙的细菌负荷略有增加.因此，当使用适当的抗生素时，细菌性肺炎早期的肺损伤部分由中性粒细胞介导。在细菌性肺炎的早期阶段，中性粒细胞有助于肺损伤的严重程度，尽管他们也参加了东道主的防守。
