Chronic Alcohol Ingestion Impairs Rat Alveolar Macrophage Phagocytosis via Disruption of RAGE Signaling
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Background Alcohol significantly impairs antioxidant defenses and innate immune function in the lung and increases matrix metalloproteinase 9 (MMP-9) activity. The receptor for advanced glycation end products (RAGE) is a well-characterized marker of lung injury that is cleaved by MMP-9 into soluble RAGE and has not yet been examined in the alcoholic lung. We hypothesized that chronic alcohol ingestion would impair RAGE signaling via MMP-9 in the alveolar macrophage and thereby impair innate immune function.Materials and methods Primary alveolar macrophages were isolated from control-fed or alcohol-fed rats. Real-time polymerase chain reaction (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assays were performed to evaluate RAGE expression. Silencing of MMP-9 ribonucleic acid (RNA) in a rat alveolar macrophage cell line was confirmed by qRT-PCR, and immunofluorescence (IF) was used to assess the association between alcohol, MMP-9, and RAGE. Phagocytosis was assessed using flow cytometry. Sulforaphane and glutathione were used to assess the relationship between oxidative stress and RAGE.Results RAGE messenger RNA expression was significantly increased in the alveolar macrophages of alcohol-fed rats, but IF showed that membrane-bound RAGE protein expression was decreased. Lavage fluid demonstrated increased levels of soluble RAGE (sRAGE). Decreasing MMP-9 expression using si-MMP-9 abrogated the effects of alcohol on RAGE protein. Phagocytic function was suppressed by direct RAGE inhibition, and the impairment was reversed by antioxidant treatment.Conclusions Chronic alcohol ingestion reduces RAGE protein expression and increases the amount of sRAGE in alveolar lavage fluid, likely via cleavage by MMP-9. In addition, it impairs phagocytic function. Antioxidants restore membrane-bound RAGE and phagocytic function.
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Ethanol exposure can increase soluble RAGE expression in bronchoalveolar lavage fluid together with RAGE ligand HMGB1 in inflammatory lung.
“In addition to adduct formation, ethanol exposure can increase soluble RAGE expression in bronchoalveolar lavage fluid together with RAGE ligand (HMGB1) in the inflammatory lung239,240.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [239]
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Deane, R., Singh, I., Sagare, A. P., Bell, R. D., Ross, N. T., LaRue, B., Love, R., Perry, S., Paquette, N., Deane, R. J., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58642 · Cited by 619 · see citing works
Receptor for Advanced Glycation End-Products is a Marker of Type I Cell Injury in Acute Lung Injury
Uchida, T., Shirasawa, M., Ware, L. B., 小島, 勝., Hata, Y., Makita, K., Mednick, G., Matthay, Z. A., & Matthay, M. A. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200509-1477oc · Cited by 468 · see citing works
Alcohol, Immunosuppression, and the Lung
Happel, K. I., & Nelson, S. (2005) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200507-065js · Cited by 208 · see citing works
Jin, X., Yao, T., Zhou, Z., Zhu, J., Zhang, S., Hu, W., & Shen, C. (2015) · BioMed Research International · doi:10.1155/2015/732450 · Cited by 173 · see citing works
Jabaudon, M., Futier, E., Roszyk, L., Chalus, E., Guerin, R., Petit, A., Mrozek, S., Perbet, S., Cayot-Constantin, S., Chartier, C., et al. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e318206b3ca · Cited by 137 · see citing works
The alcoholic lung: epidemiology, pathophysiology, and potential therapies
Joshi, P. C., & Guidot, D. M. (2007) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00348.2006 · Cited by 118 · see citing works
Self-citationReynaert, N. L., Gopal, P., Rutten, E. P. A., Wouters, E. F. �., & Schalkwijk, C. G. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.06.016 · Cited by 111 · see citing works
Joshi, P. C., Applewhite, L., Ritzenthaler, J. D., Roman, J., Fernandez, A. L., Eaton, D. C., Brown, L. A. S., & Guidot, D. M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6837 · Cited by 97 · see citing works
Self-citationAlcoholism Causes Alveolar Macrophage Zinc Deficiency and Immune Dysfunction
Mehta, A. J., Yeligar, S. M., Elon, L., Brown, L. A. S., & Guidot, D. M. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201301-0061oc · Cited by 93 · see citing works
Self-citationLois, M., BROWN, L. A. S., Moss, I. M., et al. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.160.4.9811060 · Cited by 91 · see citing works
Brown, L. A. S., Harris, F. L., Bechara, R. I., et al. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2001.tb02320.x · Cited by 81 · see citing works
Alcohol Abuse, the Alveolar Macrophage and Pneumonia
Mehta, A. J., Guidot, D. M., & Weber, K. T. (2012) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e31823ede77 · Cited by 72 · see citing works
Self-citationMehta, A. J., Joshi, P. C., Fan, X., et al. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01488.x · Cited by 62 · see citing works
Self-citationYeligar, S. M., Harris, F. L., Hart, C. M., & Brown, L. A. S. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00159.2013 · Cited by 60 · see citing works
Chen, Y., Huang, X., Yu, N., Xie, Y., Zhang, K., Wen, F., Liu, H., & Di, Q. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140918 · Cited by 51 · see citing works
Chronic Alcohol Ingestion Exacerbates Lung Epithelial Barrier Dysfunction in HIV-1 Transgenic Rats
Fan, X., Joshi, P. C., Koval, M. H., et al. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01531.x · Cited by 49 · see citing works
Self-citationJensen, J. S., Fan, X., & Guidot, D. M. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0334oc · Cited by 41 · see citing works
Self-citationYeligar, S. M., Mehta, A. J., Harris, F. L., Brown, L. A. S., & Hart, C. M. (2015) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2015-0077oc · Cited by 35 · see citing works
Moss, M. M., Steinberg, K. P., Guidot, D. M., et al. (1999) · CHEST Journal · doi:10.1378/chest.116.suppl_1.97s · Cited by 31 · see citing works
Self-citationCurry‐McCoy, T. V., Venado, A. E., Guidot, D. M., & Joshi, P. C. (2013) · Respiratory Research · doi:10.1186/1465-9921-14-39 · Cited by 27 · see citing works
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Rungratanawanich, W., Qu, Y., Wang, X., Essa, M. M., & Song, B.-J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00561-7 · Cited by 411 · see citing works
Prantner, D., Nallar, S., & Vogel, S. N. (2020) · The FASEB Journal · doi:10.1096/fj.202002136r · Cited by 92 · see citing works
- Authors
- Staitieh, B. S., Egea, E. E., Fan, X., Amah, A., & Guidot, D. M.
- Affiliations
- Emory University (US)
- Morehouse School of Medicine (US)
- Corresponding author
- Staitieh, Bashar S.
- Venue
- The American Journal of the Medical Sciences
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 355
- Issue
- 5
- Pages
- 497-505
- ISSN
- 0002-9629 (ISSN-L)
- PMC
- PMC5951623
- OpenAlex
- W2789659660
- Cited by
- 18
- References
- 21
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 1
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The American Journal of the Medical Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX001786)
- National Institute on Alcohol Abuse and Alcoholism (K08AA024512, R01AA017627)
- National Heart, Lung, and Blood Institute (R01HL144478, T32HL116271)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- chronic alcohol consumption, alveolar macrophages, phagocytosis, receptor for advanced glycation end products, RAGE signaling, MMP-9, soluble RAGE, oxidative stress, antioxidants, glutathione, sulforaphane, lung innate immunity
- MeSH terms
- Receptor for Advanced Glycation End Products, Ethanol, Alcoholism, Animals, Cells, Cultured, Immunity, Innate, Male, Phagocytosis, Signal Transduction, Macrophages, Alveolar, Rats, Sprague-Dawley, Matrix Metalloproteinase 9, Rats
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