Macrophage inducible nitric oxide synthase circulates inflammation and promotes lung carcinogenesis

Xin Wang, Zane Gray, Jami Willette-Brown, Feng Zhu, Gongping Shi, Qun Jiang, Na Young Song, Liang Dong, Yinling Hu

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Human lung squamous cell carcinoma (SCC) is highly associated with increased pulmonary macrophage infiltration. Previously, we showed that marked pulmonary infiltrating macrophages were required for spontaneous lung SCC development in a mouse model (L-IkkαKA/KA, KA/KA) that resembles human lung SCC. Interestingly the lung SCC-associated macrophages specifically express elevated inducible nitric oxide synthase (NOS2). However, the role of macrophage NOS2 in lung carcinogenesis has not been explored. Here, we show that NOS2 ablation inhibits macrophage infiltration, fibrosis, and SCC development in the lungs of KA/KA mice. Macrophage NOS2 was found to circulate inflammation and enhance macrophage migration and survival. NOS2 promotes foamy macrophage formation characterized with impaired lipid metabolism. NOS2 null bone marrow transplantation reduces foamy macrophage numbers and carcinogenesis in KA/KA chimaeras. This finding sheds light on a new mechanism by which macrophage NOS2 increases pulmonary inflammatory responses and macrophage survival and impairs macrophage lipid metabolism, thereby promoting lung SCC formation.

Original languageEnglish
Article number46
JournalCell Death Discovery
Issue number1
Publication statusPublished - 2018 Dec 1

Bibliographical note

Funding Information:
This work was supported by funding from the National Cancer Institute (ZIA BC011212, and ZIA BC 011391) to Y.H. We thank Zuoxiang Xiao from the National Cancer Institute for technical instructions.

Publisher Copyright:
© 2018, The Author(s).

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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