Human alveolar macrophages do not rely on glucose metabolism upon activation by lipopolysaccharide

Pereverzeva, Liza; Linge, Christine C. A. van; Schuurman, Alex R.; Klarenbeek, Augustijn M.; Ramirez‐Moral, Ivan; Otto, Natasja A.; Peters‐Sengers, Hessel; Butler, Joe; Schomakers, Bauke V.; Weeghel, Michel van; Houtkooper, Riekelt H.; Wiersinga, W. Joost; Bonta, Peter I.; Annema, Jouke T.; Vos, Alex F. de; Poll, Tom van der

doi:10.1016/j.bbadis.2022.166488

Cited by 13 publications

(13 citation statements)

References 31 publications

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“…In contrast to MDM, AML cells did not respond to LPS to induce glycolysis (Fig. 5N), similar to a previous finding reported in human AMs (34). Mitochondrial mass, mitochondrial membrane potential, the rate of proton leak, oxygen consumption, and ATP synthesis dynamically influence mitochondrial ROS production (41).…”

Section: Aml Cells Have Upregulated Lipid Uptake Genes and A Drive To...supporting

confidence: 87%

“…5B). Further, like reported for HAM (33,34), we observed that AML cells exhibited much higher basal and maximal oxygen consumption rate (39)(OCR) compared with MDM, signifying the engagement of OxPhos and mitochondrial activities (Fig. 5C).…”

Section: Aml Cells Have Upregulated Lipid Uptake Genes and A Drive To...supporting

confidence: 84%

“…Both AML and MDM cells demonstrated very limited proliferation capacity as has been described for healthy adult HAMs (27,28). In contrast to MDM, AML cells did not respond to LPS to induce glycolysis, as reported for HAM (34). Although, previous data also suggest that virulent M.tb can drive the shift towards aerobic glycolysis in HAM (39).…”

Section: Discussionsupporting

confidence: 55%

“…The lung alveolar space is rich in surfactant proteins and lipids, and has low levels of glucose (32,33), an environment that may be conducive to the known low immunoreactivity of AMs, representing an adaptation to their specific environment. AMs engage in OxPhos over glycolysis as their core source of ATP (34), a finding in both human and murine cellular studies. Patients suffering from sepsis endure a shift from OxPhos to aerobic glycolysis, which is reversed upon patient recovery (35).…”

Section: Aml Cells Have Upregulated Lipid Uptake Genes and A Drive To...mentioning

confidence: 99%

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A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases

Pahari

Arnett

Simper

et al. 2023

Preprint

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Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAM) to pulmonary diseases remains poorly understood due to difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, i.e., Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (GM-CSF, TGF-β, and IL-10) that facilitate the conversion of blood-obtained monocytes to an AM-Like (AML) phenotype and function in tissue culture. Similar to HAM, AML cells are particularly susceptible to both Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study reveals the importance of alveolar space components in the development and maintenance of HAM phenotype and function, and provides a readily accessible model to study HAM in infectious and inflammatory disease processes, as well as therapies and vaccines.

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Section: Aml Cells Have Upregulated Lipid Uptake Genes and A Drive To...supporting

confidence: 87%

Section: Aml Cells Have Upregulated Lipid Uptake Genes and A Drive To...supporting

confidence: 84%

Section: Discussionsupporting

confidence: 55%

Section: Aml Cells Have Upregulated Lipid Uptake Genes and A Drive To...mentioning

confidence: 99%

See 2 more Smart Citations

A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases

Pahari

Arnett

Simper

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Indeed, tissue-resident macrophages may have strikingly different metabolic patterns as compared to BMDMs. Thus, murine and human alveolar macrophages have low rates of glycolysis, which are not increased following LPS stimulation ( 48 , 49 ). Consequently, alveolar macrophages are highly dependent on oxidative phosphorylation for the production of inflammatory mediators in response to LPS.…”

Section: Discussionmentioning

confidence: 99%

Rapid glycolytic activation accompanying innate immune responses: mechanisms and function

Namgaladze

Brüne

2023

Front. Immunol.

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Innate immune responses to pathogens, mediated by activation of pattern recognition receptors and downstream signal transduction cascades, trigger rapid transcriptional and epigenetic changes to support increased expression of pro-inflammatory cytokines and other effector molecules. Innate immune cells also rapidly rewire their metabolism. The most prominent metabolic alteration following innate immune activation is rapid up-regulation of glycolysis. In this mini-review, we summarize recent advances regarding the mechanisms of rapid glycolytic activation in innate immune cells, highlighting the relevant signaling components. We also discuss the impact of glycolytic activation on inflammatory responses, including the recently elucidated links of metabolism and epigenetics. Finally, we highlight unresolved mechanistic details of glycolytic activation and possible avenues of future research in this area.

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Immunometabolism at the basis of health and disease; an editorial

Bossche¹,

Horng²,

Ryan³

2023

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Human alveolar macrophages do not rely on glucose metabolism upon activation by lipopolysaccharide

Cited by 13 publications

References 31 publications

A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases

A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases

Rapid glycolytic activation accompanying innate immune responses: mechanisms and function

Immunometabolism at the basis of health and disease; an editorial

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