Article Open Access

Glutamine Metabolism Is Required for Alveolar Macrophage Proliferation

Journal of Respiratory Biology and Translational Medicine . 2024, 1(1), 10004;
Min Wang 1,2    Bibo Zhu 2,3,4    Cheng Zhang 5    Chaofan Li 2,3,4    Ruixuan Zhang 2,3,4    Jeffery Rathmell 6    Hu Li 5    Weiguo Cui 7    Taro Hitosugi 5    Jie Sun 2,3,4 *   
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA
Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA
Vanderbilt Center for Immunobiology, Departments of Pathology, Microbiology, and Immunology, Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Versiti, Blood Research Institute, Milwaukee, WI 53226, USA
Authors to whom correspondence should be addressed.

Received: 24 Feb 2024    Accepted: 25 Mar 2024    Published: 28 Mar 2024   


Alveolar macrophages (AMs) are critical for normal lung homeostasis, surfactant metabolism, and host defense against various respiratory pathogens. Despite being terminally differentiated cells, AMs are able to proliferate and self-renew to maintain their compartment without the input of the hematopoietic system in the adulthood during homeostasis. However, the molecular and metabolic mechanisms modulating AM proliferative responses are still incompletely understood. Here we have investigated the metabolic regulation of AM proliferation and self-renewal. Inhibition of glucose uptake or fatty acid oxidation did not significantly impact AM proliferation. Rather, inhibition of the glutamine uptake and/or glutaminase activity impaired AM mitochondrial respiration and cellular proliferation in vitro and in vivo in response to growth factor stimulation. Furthermore, mice with a genetic deletion of glutaminase in macrophages showed decreased proliferation. Our data indicate that glutamine is a critical substrate for fueling mitochondrial metabolism that is required for AM proliferation. Overall, our study is expected to shed light on the AM maintenance and repopulation by glutamine during homeostasis and following acute respiratory viral infection.


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