ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Hypercapnia Inhibits Autophagy and Bacterial Killing in Human Macrophages by Increasing Expression of Bcl-2 and Bcl-xL.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
- Autophagic flux blockade under hypocapnia reveals CO2-sensitive regulation of autophagy-lysosome homeostasis.Biology open · 2026Article
- Hypercapnia Effects on Lung Function.Comprehensive Physiology · 2026Review
- Inflammatory discordance phenotype in COPD: Dissociation between neutrophil-to-lymphocyte ratio and conventional markers.PloS one · 2026Article
- A novel phage vB_VhaM_HVS-1 inhibits host cell associatedFrontiers in veterinary science · 2026Article
- Long-term DNA methylation changes induced by age and elevated COSkeletal muscle · 2025Article
- Hypercapnia as a Double-Edged Modulator of Innate Immunity and Alveolar Epithelial Repair: A PRISMA-ScR Scoping Review.International journal of molecular sciences · 2025Article
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- Rapamycin improves satellite cells' autophagy and muscle regeneration during hypercapnia.JCI insight · 2025Article
- Hypercapnic acidosis affectsFrontiers in cellular and infection microbiology · 2025Article
- Influence of the spaceflight environment on macrophage lineages.NPJ microgravity · 2024Review
- Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia.International journal of molecular sciences · 2024Article
- Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.JCI insight · 2024Article
- Lowering PRespiratory care · 2023Article
- Carbon dioxide and MAPK signalling: towards therapy for inflammation.Cell communication and signaling : CCS · 2023Review
- Hypercapnia increases ACE2 expression and pseudo-SARS-CoV-2 entry in bronchial epithelial cells by augmenting cellular cholesterol.Frontiers in immunology · 2023Article
- The molecular regulation of autophagy in antimicrobial immunity.Journal of molecular cell biology · 2022Article
- The functional mechanism of bone marrow-derived mesenchymal stem cells in the treatment of animal models with Alzheimer's disease: crosstalk between autophagy and apoptosis.Stem cell research & therapy · 2022Review
- Elevated COInterface focus · 2021Review
- Hypercapnia selectively modulates LPS-induced changes in innate immune and DNA replication-related gene transcription in the macrophage.Interface focus · 2021Article
- Mechanisms of Hypercapnia-Induced Endoplasmic Reticulum Dysfunction.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Hypercapnia, the elevation of CO2 in blood and tissue, commonly develops in patients with advanced lung disease and severe pulmonary infections, and it is associated with high mortality. We previously reported that hypercapnia alters expression of host defense genes, inhibits phagocytosis, and increases the mortality of Pseudomonas pneumonia in mice. However, the effect of hypercapnia on autophagy, a conserved process by which cells sequester and degrade proteins and damaged organelles that also plays a key role in antimicrobial host defense and pathogen clearance, has not previously been examined. In the present study we show that hypercapnia inhibits autophagy induced by starvation, rapamycin, LPS, heat-killed bacteria, and live bacteria in the human macrophage. Inhibition of autophagy by elevated CO2 was not attributable to acidosis. Hypercapnia also reduced macrophage killing of Pseudomonas aeruginosa. Moreover, elevated CO2 induced the expression of Bcl-2 and Bcl-xL, antiapoptotic factors that negatively regulate autophagy by blocking Beclin 1, an essential component of the autophagy initiation complex. Furthermore, small interfering RNA targeting Bcl-2 and Bcl-xL and the small molecule Z36, which blocks Bcl-2 and Bcl-xL binding to Beclin 1, prevented hypercapnic inhibition of autophagy and bacterial killing. These results suggest that targeting the Bcl-2/Bcl-xL-Beclin 1 interaction may hold promise for ameliorating hypercapnia-induced immunosuppression and improving resistance to infection in patients with advanced lung disease and hypercapnia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.