Macrophage‐1 antigen exacerbates histone‐induced acute lung injury and promotes neutrophil extracellular trap formation

TL;DR

This study shows that Mac-1 antigen worsens lung injury caused by histones and increases the formation of neutrophil traps, especially when platelets are activated.

Contribution

The study reveals a novel role of Mac-1 in histone-induced acute lung injury and NET formation.

Findings

Mac-1 deficiency improved survival and reduced lung damage in histone-treated mice.

Mac-1−/− mice showed decreased platelet-leukocyte aggregates and plasma myeloperoxidase levels.

NET formation was significantly lower in Mac-1−/− neutrophils compared to wild-type.

Abstract

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.

Macrophage‐1 antigen (Mac‐1) deficiency ameliorated histone‐induced acute lung injury (ALI) and myeloperoxidase elevation in plasma, and decreased the formation of neutrophil extracellular trap (NET)‐like chromatin fibers in the presence of activated platelets. Thus, Mac‐1 is associated with the exacerbation of histone‐induced ALI and the promotion of NET formation in the presence of activated platelets.

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