Macrophage inducible nitric oxide synthase circulates inflammation and promotes lung carcinogenesis

Cell Death Discovery
Xin WangYinling Hu

Abstract

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-Ikkα KA/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.

References

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Citations

Jan 27, 2019·The Journal of Pathology·Simon MiletteDaniela F Quail
Dec 11, 2019·Diagnostics·Antonia HarangușMărioara Șimon
Oct 2, 2020·Journal of Receptor and Signal Transduction Research·Bo ZhangGuoping Chen
Sep 19, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Yan HuangXueping Zhou
Jul 25, 2020·Journal of Applied Microbiology·A R BalasubramanianP Neelakantan
Nov 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mariusz G FleszarMałgorzata Krzystek-Korpacka
Jan 16, 2020·Immunity·Jérôme Galon, Daniela Bruni
Jan 8, 2021·Cell and Tissue Research·Denusha ShresthaChandrashekhar Charavaryamath

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Datasets Mentioned

BETA
GSE101759

Methods Mentioned

BETA
flow cytometry
PCR
FCS
Assay

Software Mentioned

Partek Genomics Suite
Nikon

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