ArticleFrontiers in immunology2022
Signaling Pathways That Mediate Alveolar Macrophage Activation by Surfactant Protein A and IL-4.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 18 citations in OpenAlex.
- Transient receptor potential vanilloid 4 (TRPV4) channels mediate pulmonary surfactant protein A and D secretion.American journal of respiratory cell and molecular biology · 2026Article
- Altered AP-1, RUNX, and EGR chromatin dynamics drive human fibrotic lung disease.Annals of the rheumatic diseases · 2026Article
- Epimedin C attenuates airway inflammation and remodeling in Asthma by intervening M2 macrophage polarization via modulating the PI3K/Akt/mTOR signaling pathway.Scientific reports · 2026Article
- Peroxiredoxin 4 as a switch regulating PTEN/AKT axis in alveolar macrophages activation.Signal transduction and targeted therapy · 2025Article
- Role of Colony Stimulating Factor 1 (CSF-1) and Its Receptor CSF1R: Macrophage Repolarization for Glioblastoma Treatment.ACS pharmacology & translational science · 2025Review
- Extracellular Vesicles in the Mesenchymal Stem Cell/Macrophage Axis: Potential Targets for Inflammatory Treatment.International journal of molecular sciences · 2025Review
- Lung epithelial and alveolar macrophage-like cell interactions significantly modify innate responses to bacterial endotoxin with the involvement of direct cellular contacts, TNF-α, ICAM1 and MCP-1.Frontiers in immunology · 2025Article
- Dissecting metabolic landscape of alveolar macrophage.Scientific reports · 2024Article
- Immunometabolic Signature during Respiratory Viral Infection: A Potential Target for Host-Directed Therapies.Viruses · 2023Review
- Interaction between alveolar macrophages and epithelial cells duringFrontiers in cellular and infection microbiology · 2023Review
- Surfactant protein A alters endosomal trafficking of influenza A virus in macrophages.Frontiers in immunology · 2023Article
- Tumour-associated macrophages: versatile players in the tumour microenvironment.Frontiers in cell and developmental biology · 2023Review
- Plasticity towards Rigidity: A Macrophage Conundrum in Pulmonary Fibrosis.International journal of molecular sciences · 2022Review
- Extracellular traps and the role in thrombosis.Frontiers in cardiovascular medicine · 2022Review
- The collectin SP-A and its trimeric recombinant fragment protect alveolar epithelial cells from the cytotoxic and proinflammatory effects of human cathelicidinFrontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of tissue repair program in macrophages requires the integration of IL-4/IL-13 cytokines and tissue-specific signals. In the lung, surfactant protein A (SP-A) is a tissue factor that amplifies IL-4Rα-dependent alternative activation and proliferation of alveolar macrophages (AMs) through the myosin18A receptor. However, the mechanism by which SP-A and IL-4 synergistically increase activation and proliferation of AMs is unknown. Here we show that SP-A amplifies IL-4-mediated phosphorylation of STAT6 and Akt by binding to myosin18A. Blocking PI3K activity or the myosin18A receptor abrogates SP-A´s amplifying effects on IL-4 signaling. SP-A alone activates Akt, mTORC1, and PKCζ and inactivates GSK3α/β by phosphorylation, but it cannot activate arginase-1 activity or AM proliferation on its own. The combined effects of IL-4 and SP-A on the mTORC1 and GSK3 branches of PI3K-Akt signaling contribute to increased AM proliferation and alternative activation, as revealed by pharmacological inhibition of Akt (inhibitor VIII) and mTORC1 (rapamycin and torin). On the other hand, the IL-4+SP-A-driven PKCζ signaling axis appears to intersect PI3K activation with STAT6 phosphorylation to achieve more efficient alternative activation of AMs. Consistent with IL-4+SP-A-driven activation of mTORC1 and mTORC2, both agonists synergistically increased mitochondrial respiration and glycolysis in AMs, which are necessary for production of energy and metabolic intermediates for proliferation and alternative activation. We conclude that SP-A signaling in AMs activates PI3K-dependent branched pathways that amplify IL-4 actions on cell proliferation and the acquisition of AM effector functions.
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