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

Tomohiro Mizuno, Fumihiko Nagano, Kazuo Takahashi, Shigeki Yamada, Kazuhiro Fruhashi, Shoichi Maruyama, Naotake Tsuboi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)574-583
Number of pages10
JournalFEBS Open Bio
Issue number4
Publication statusPublished - 04-2024

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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