Acute lung injury (ALI), which occurs in association with sepsis, trauma, and coronavirus disease 2019 (COVID-19), is a serious clinical condition with high mortality. Excessive platelet-leukocyte aggregate (PLA) formation promotes neutrophil extracellular trap (NET) release and thrombosis, which are involved in various diseases, including ALI. Macrophage-1 antigen (Mac-1, CD11b/CD18), which is expressed on the surface of leukocytes, is known to promote NET formation. This study aimed to elucidate the role of Mac-1 in extracellular histone-induced ALI. Exogenous histones were administered to Mac-1-deficient mice and wild-type (WT) mice with or without neutrophil or platelet depletion, and several parameters were investigated 1 h after histone injection. Depletion of neutrophils or platelets improved survival time and macroscopic and microscopic properties of lung tissues, and decreased platelet-leukocyte formation and plasma myeloperoxidase levels. These improvements were also observed in Mac-1^−/− mice. NET formation in Mac-1^−/− bone marrow neutrophils (BMNs) was significantly lower than that in WT BMNs. In conclusion, our findings suggest that Mac-1 is associated with exacerbation of histone-induced ALI and the promotion of NET formation in the presence of activated platelets.

中文翻译：

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巨噬细胞1抗原加剧组蛋白诱导的急性肺损伤并促进中性粒细胞胞外陷阱形成

急性肺损伤 (ALI) 与脓毒症、创伤和 2019 年冠状病毒病 (COVID-19) 相关，是一种严重的临床疾病，死亡率很高。过多的血小板白细胞聚集体 (PLA) 形成会促进中性粒细胞胞外陷阱 (NET) 释放和血栓形成，这与包括 ALI 在内的多种疾病有关。巨噬细胞 1 抗原（Mac-1、CD11b/CD18）在白细胞表面表达，已知可促进 NET 形成。本研究旨在阐明 Mac-1 在细胞外组蛋白诱导的 ALI 中的作用。将外源组蛋白给予 Mac-1 缺陷型小鼠和有或没有中性粒细胞或血小板消耗的野生型 (WT) 小鼠，并在组蛋白注射后 1 小时研究几个参数。中性粒细胞或血小板的消耗改善了肺组织的存活时间和宏观和微观特性，并减少了血小板白细胞形成和血浆髓过氧化物酶水平。在 Mac-1 ^−/−小鼠中也观察到了这些改进。 Mac-1 ^−/−骨髓中性粒细胞 (BMN) 中的 NET 形成显着低于 WT BMN。总之，我们的研究结果表明，Mac-1 与组蛋白诱导的 ALI 的恶化以及活化血小板存在下促进 NET 的形成有关。