Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS‐induced acute lung injury

Bivona, Joseph J.; Crymble, Hanna M.; Guigni, Blas A.; Stapleton, Renee D.; Files, D. Clark; Toth, Michael J.; Poynter, Matthew E.; Suratt, Benjamin T.

doi:10.1096/fj.202002275rr

Cited by 10 publications

(11 citation statements)

References 55 publications

(106 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…Our model of acute endotoxemia mimics sepsis-like cytokine pathology and was derived from a model of IT LPS administration ( Bivona et al, 2021 ). Lung leakage following injury allowed LPS to enter circulation and was measured systemically shortly after administration of the injurious LPS dose ( Bivona et al, 2021 ). Therefore, to decrease potential confounding effects of lung injury, we used these measured systemic LPS values after IT LPS for our IV injections in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…While this and other studies measure decreases in systemic cytokine production in response to muscle-specific knockout of inflammatory sensors/signaling molecules/cytokines, they are unable to determine whether these effects are related solely to skeletal muscle release, or if other cell crosstalk intermediates are involved. Our earlier in vitro studies revealed the amplifying effects of macrophage derived TNF on LPS-induced pro-inflammatory cytokine production from co-cultured C2C12 myotubes ( Bivona et al, 2021 ). The unchanged gene expression of gastrocnemius Tnf and systemic concentrations of TNFα suggest that this mechanism is still in play in our knockout models.…”

Section: Discussionmentioning

confidence: 99%

“…To model acute endotoxemia, we administered 1.5 μg (1.0 μg per ml of blood volume, calculated to be approximately 1.5 ml per mouse ( NC3RS, 2022 )) of ultrapure O55:B5 lipopolysaccharide (Invivogen, San Diego, CA) in saline intravenously to mice via the retroorbital sinus. This LPS concentration was derived by determining in previous studies the leakage of LPS into the bloodstream subsequent to IT administration of 3 μg LPS/g in our mouse model of acute lung injury ( Bivona et al, 2021 ). Validation of the IV LPS model was first performed in wild type mice that were administered IV saline vehicle or IV LPS followed by gastrocnemius muscle gene expression quantitation 3 h later, at which time mice were euthanized by an IP injection of 150 mg/kg pentobarbital (Euthasol, Midwest Veterinary Supply, Lakeville, MN).…”

Section: Methodsmentioning

confidence: 99%

“…Using a model of acute lung injury, our recent work showed that muscle potently expresses and releases several pro-inflammatory cytokines and is synergized by macrophages ( Bivona et al, 2021 ). In this model, bacterial LPS is delivered intratracheally, causing cellular influx to the lung between 6 and 12 h, which persists for several days.…”

Section: Introductionmentioning

confidence: 99%

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Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone

et al. 2022

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The abundance, anatomical distribution, and vascularity of skeletal muscle make it a potentially important contributor to local cytokine production and systemic cytokine abundance during inflammatory events. An orchestrated balance between the production of pro- and anti-inflammatory mediators is necessary for proper immune function, yet the contribution of the body’s largest organ system, comprised primarily of skeletal muscle myocytes that fuse to form myofibers, to this process is largely unknown. Endotoxin (lipopolysaccharide, LPS) stimulates toll-like receptor 4 (TLR4) to induce the production of several pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2), by a of myriad cell types. We sought to quantify the influence of myofibers on systemic cytokine concentrations following an acute endotoxemia challenge. To accomplish this, we generated muscle specific conditional knockouts for TLR4 (TLR4SMKO), IL-6 (IL6SMKO), and CCL2 (CCL2SMKO). We administered low concentrations of intravenous LPS (IV LPS) to these receptor and effector knockout mice and collected samples after 3 h. Using gene expression analysis of gastrocnemius muscle and serum cytokine measurements after IV LPS, we determined that deletion of myofiber IL-6 or CCL2 led to a 93% and 57% reduction of these specific cytokines in the systemic circulation, respectively. Myofiber specific TLR4 deletion decreased the expression of IL-6, CCL2, and C-X-C motif chemokine ligand 1 (CXCL1) in the gastrocnemius muscle. These data indicate the critical involvement and direct contribution of myofibers during the early systemic inflammatory cytokine response to endotoxin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone

et al. 2022

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Inotodiol, an antiasthmatic agent with efficacy and safety, preferentially impairs membrane-proximal signaling for mast cell activation

Liu

Naskar

Acharya

et al. 2023

International Immunopharmacology

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Tissue-Resident Immune Cells in Humans

Gray

Farber

2022

Annu. Rev. Immunol.

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Tissue-resident immune cells span both myeloid and lymphoid cell lineages, have been found in multiple human tissues, and play integral roles at all stages of the immune response, from maintaining homeostasis to responding to infectious challenges to resolution of inflammation to tissue repair. In humans, studying immune cells and responses in tissues is challenging, although recent advances in sampling and high-dimensional profiling have provided new insights into the ontogeny, maintenance, and functional role of tissue-resident immune cells. Each tissue contains a specific complement of resident immune cells. Moreover, resident immune cells for each lineage share core properties, along with tissue-specific adaptations. Here we propose a five-point checklist for defining resident immune cell types in humans and describe the currently known features of resident immune cells, their mechanisms of development, and their putative functional roles within various human organs. We also consider these aspects of resident immune cells in the context of future studies and therapeutics. Expected final online publication date for the Annual Review of Immunology, Volume 40 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS‐induced acute lung injury

Cited by 10 publications

References 55 publications

Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone

Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone

Inotodiol, an antiasthmatic agent with efficacy and safety, preferentially impairs membrane-proximal signaling for mast cell activation

Tissue-Resident Immune Cells in Humans

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