Acute Respiratory Distress Syndrome is associated with impaired alveolar macrophage efferocytosis
Acute Respiratory Distress Syndrome is associated with impaired alveolar macrophage efferocytosis
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急性呼吸窘迫综合征与肺泡巨噬细胞胞吞作用受损有关
DOI：
10.1101/2021.03.15.21253591
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Mahida R
中科院分区：
文献类型：
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作者：
Mahida R
急性呼吸窘迫综合征（ARDS）是一种以脓毒症为主要病因的肺部炎症性疾病。尽管通气策略取得了进展，但中度至重度ARDS的死亡率仍为40-46% [1]。ARDS与中性粒细胞流入肺泡有关。支气管肺泡灌洗液（BAL）中中性粒细胞数量持续升高和肺泡巨噬细胞（AM）数量持续降低与死亡率升高相关[2]。虽然早期ARDS的炎性肺泡环境最初延迟了细胞凋亡，但这些中性粒细胞最终在肺泡内发生细胞凋亡[3]。AM对凋亡中性粒细胞的有效抑制作用对于炎症的消退至关重要[3]。由于有缺陷的AM红细胞增多和/或过度的红细胞增多能力，凋亡中性粒细胞可能在ARDS中积聚，然后发生继发性坏死，将炎症介质释放到肺泡腔中[4]。这可能有助于在ARDS中观察到的长期炎症。以前没有研究评估过ARDS患者的AM巨噬细胞增多症;然而，来自ARDS患者的单核细胞衍生的巨噬细胞（MDM）确实存在受损的AM巨噬细胞增多症[5]。我们研究了ARDS患者是否存在AM细胞增多受损和肺泡中性粒细胞凋亡增加。
Acute respiratory distress syndrome (ARDS) is an inflammatory disorder of the lungs, with sepsis as the predominant aetiology. Despite advances in ventilation strategies, mortality for moderate to severe ARDS remains at 40–46% [1]. ARDS is associated with neutrophil influx into alveoli. Persistently high neutrophil and low alveolar macrophage (AM) numbers in bronchoalveolar lavage (BAL) fluid are associated with greater mortality [2]. While the inflammatory alveolar environment of early ARDS initially delays apoptosis, these neutrophils ultimately undergo apoptosis within alveoli [3]. Efficient efferocytosis of apoptotic neutrophils by AMs is critical for resolution of inflammation [3]. Apoptotic neutrophils may accumulate in ARDS due to defective AM efferocytosis and/or overwhelmed efferocytosis capacity, then undergo secondary necrosis, releasing inflammatory mediators into the alveolar space [4]. This may contribute to the prolonged inflammation observed in ARDS. No study has previously assessed AM efferocytosis in ARDS; however, monocyte-derived macrophages (MDMs) from ARDS patients do have impaired efferocytosis [5]. We investigated whether ARDS patients have impaired AM efferocytosis and increased alveolar neutrophil apoptosis.