Supplementary Material for: CCR5 and FPR1 Mediate Neutrophil Recruitment in Endotoxin-Induced Lung Injury

Recruitment of neutrophils, regarded as a key mechanism in acute lung injury (ALI), is orchestrated by cell adhesion molecules and chemokines. While the importance of cell adhesion molecules has been carefully investigated, little is known about the importance of chemokines and their receptors in the recruitment of neutrophils in models of ALI. Wild-type <i>Ccr2</i>^<i>-/-</i>,<i> Ccr5</i>^<i>-/-</i>,<i> Fpr1</i>^<i>-/-</i> or <i>Fpr2</i>^<i>-/-</i> mice were exposed to aerosolized lipopolysaccharide and the number of neutrophils in the lung tissue (intravascular, interstitial) and in the bronchoalveolar lavage was quantified. Lack of CCR5 or FPR1, but not CCR2 or FPR2, significantly reduced lung neutrophil infiltration in all compartments. Similarly, blockade of CCR5 or FPR1 with specific antagonists reduced counts of alveolar, interstitial and intravascular neutrophils. Such treatments also inhibited lung edema formation and histological lung tissue alterations, thus underscoring the protective role of CCR5 and FPR1 neutralizing strategies in ALI.

中性粒细胞募集被视为急性肺损伤（acute lung injury, ALI）的核心发病机制，由细胞黏附分子（cell adhesion molecules）与趋化因子（chemokines）协同调控。尽管学界已对细胞黏附分子的重要性开展了充分研究，但目前对于急性肺损伤模型中趋化因子及其受体在中性粒细胞募集过程中的作用仍知之甚少。研究人员将野生型<i>Ccr2</i>^<i>-/-</i>、<i>Ccr5</i>^<i>-/-</i>、<i>Fpr1</i>^<i>-/-</i>或<i>Fpr2</i>^<i>-/-</i>小鼠暴露于雾化脂多糖（lipopolysaccharide）环境中，并对肺组织（血管内、间质）及支气管肺泡灌洗液（bronchoalveolar lavage）中的中性粒细胞数量进行定量检测。实验结果表明，缺失CCR5或FPR1（而非CCR2或FPR2）可显著降低所有肺组织分区内的中性粒细胞浸润程度。同理，使用特异性拮抗剂（antagonists）阻断CCR5或FPR1，也可减少肺泡、间质及血管内的中性粒细胞计数。此类干预措施还可抑制肺水肿形成与肺组织病理学改变，由此凸显了靶向CCR5与FPR1的中和策略在急性肺损伤中的保护作用。