Fetal Alcohol Exposure Impairs Alveolar Macrophage Function via Decreased Glutathione Availability
Abstract
Immature function of the alveolar macrophage increases the risk of pulmonary infections in premature newborns. In utero alcohol increases fetal systemic oxidative stress. Because the premature lung is deficient in glutathione (GSH), we hypothesized that chronic in utero alcohol (ethanol) exposure exacerbates the oxidative stress within the developing lung, thereby impairing alveolar macrophage function. Additionally, we evaluated the effects of in vivo and in vitro GSH availability on ethanol-exposed macrophage function. Using a guinea pig model of chronic in utero ethanol exposure, fetal epithelial lining fluid (ELF) and alveolar macrophage GSH were decreased with increased markers of oxidative stress. Ethanol-exposed macrophage exhibited impaired phagocytosis and increased apoptosis compared with gestational control. When the GSH precursor S-adenosyl-methionine (SAM) was added to the maternal drinking water containing ethanol, fetal ELF and macrophage GSH were maintained and ELF oxidative stress diminished. In vivo maternal SAM therapy maintained macrophage phagocytosis and decreased apoptosis. In vitro GSH supplements also improved phagocytosis and viability in both premature and ethanol-exposed macrophage. This suggested that in utero ethanol impaired premature macrophage function and viability via decreased GSH availability. Furthermore, GSH supplementation during and after ethanol exposure improved fetal macrophage function and viability. These results add a new dimension to the detrimental effects of fetal alcohol exposure on the developing alveolar macrophage, raising the possibility of GSH therapy to augment premature alveolar macrophage function.
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Chronic and/or excessive alcohol intake can cause ARDS and other types of pulmonary dysfunction characterized by reduced air exchange rates with increased lung epithelial barrier dysfunction, possibly through increased oxidative stress and MDA and 4-HNE adducts.
“Chronic and/or excessive alcohol intake can cause acute respiratory distress syndrome (ARDS) and other types of pulmonary dysfunction characterized by reduced air exchange rates with increased lung epithelial barrier dysfunction, possibly through increased oxidative stress and MDA and 4-HNE adducts164,234.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [234]
Cites
The Maternal Lifestyle Study: Drug Use by Meconium Toxicology and Maternal Self-Report
Lester, B. M., ElSohly, M. A., Wright, L. L., Smeriglio, V. L., Verter, J. I., Bauer, C. R., Shankaran, S., Bada, H. S., Walls, H. C., Huestis, M. A., et al. (2001) · PEDIATRICS · doi:10.1542/peds.107.2.309 · Cited by 307 · see citing works
Causes of Oxidative Stress in the Pre- and Perinatal Period
Gitto, E., Reiter, R. J., Karbownik‐Lewińska, M., Tan, D., Gitto, P., Barberi, S., & Barberi, I. (2002) · Neonatology · doi:10.1159/000051527 · Cited by 272 · see citing works
Prenatal development of lung antioxidant enzymes in four species
Frank, L., & Sosenko, R. S. I. (1987) · The Journal of Pediatrics · doi:10.1016/s0022-3476(87)80300-1 · Cited by 265 · see citing works
Population-based case-control study of teratogenic potential of corticosteroids.
Czeizel, A., & Rockenbauer, M. (1997) · Teratology · doi:10.1002/(sici)1096-9926(199711)56:5 · Cited by 235 · see citing works
The Effects of Chronic Alcohol Abuse on Pulmonary Glutathione Homeostasis
Moss, M. M., Guidot, D. M., WONG-LAMBERTINA, M., Hoor, T. T., Perez, R. L., & BROWN, L. A. S. (2000) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.161.2.9905002 · Cited by 202 · see citing works
Self-citationDNA Damage, DNA Repair, and Alcohol Toxicity--A Review
Brooks, P. J. (1997) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1997.tb04256.x · Cited by 188 · see citing works
Frank, L., & Sosenko, I. R. S. (1991) · Pediatric Research · doi:10.1203/00006450-199103000-00014 · Cited by 170 · see citing works
Lundsberg, L. S., Bracken, M. B., & Saftlas, A. F. (1997) · Annals of Epidemiology · doi:10.1016/s1047-2797(97)00081-1 · Cited by 167 · see citing works
Holguín, F., Moss, I. M., Brown, L. A. S., & Guidot, D. M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1396 · Cited by 166 · see citing works
Self-citationAlcohol consumption by pregnant women in the united states during 1988–1995
Sh, E. (1998) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(98)00205-1 · Cited by 164 · see citing works
Vinitha, R., Perez, A., Chen, J., Duraisamy, S., Schenker, S., & Henderson, G. I. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2001.tb02292.x · Cited by 159 · see citing works
Reactive Oxygen Species and Preterm Premature Rupture of Membranes—A Review
Woods, J. R. (2001) · Placenta · doi:10.1053/plac.2001.0638 · Cited by 156 · see citing works
Oxidant Stress Responses in Premature Infants during Exposure to Hyperoxia
Smith, C. V., Hansen, T. N., Martin, N. E., et al. (1993) · Pediatric Research · doi:10.1203/00006450-199309000-00024 · Cited by 139 · see citing works
Oxidative stress and diabetes in pregnant rats
Damasceno, D. C., Volpato, G. T., Calderon, I. D. M. P., & Rudge, M. V. C. (2002) · Animal Reproduction Science · doi:10.1016/s0378-4320(02)00094-5 · Cited by 136 · see citing works
Roos, D., Weening, R. S., Voetman, A. A., van Schaik, M., Bot, A. A. A. M., Meerhof, L. J., & Loos, J. A. (1979) · Blood · doi:10.1182/blood.v53.5.851.851 · Cited by 133 · see citing works
Heaton, M. B., Mitchell, J. J., & Paiva, M. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb02019.x · Cited by 127 · see citing works
In Utero Ethanol Exposure Elicits Oxidative Stress in the Rat Fetus
Henderson, G. I., Devi, B. G., Perez, A., & Schenker, S. (1995) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1995.tb01572.x · Cited by 127 · see citing works
Increased rate of lipid peroxidation and protein carbonylation in experimental diabetic pregnancy
Cederberg, J., Basu, S., & Eriksson, U. J. (2001) · Diabetologia · doi:10.1007/s001250051686 · Cited by 110 · see citing works
Jain, A., Mehta, T., Auld, P. A. M., Rodrigues, J. A., Ward, R. F., Schwartz, M. K., & Mårtensson, J. (1995) · Pediatric Pulmonology · doi:10.1002/ppul.1950200306 · Cited by 109 · see citing works
Comparison of binge drinking among pregnant and nonpregnant women, United States, 1991-1995
Ebrahim, S. H., Diekman, S., Floyd, R. L., & Decouflé, P. (1999) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(99)70139-0 · Cited by 103 · see citing works
Devi, B. G., Henderson, G. I., Frosto, T. A., & Schenker, S. (1993) · Hepatology · doi:10.1002/hep.1840180325 · Cited by 96 · see citing works
Pasantes‐Morales, H., Murray, R. A., Sánchez‐Olea, R., et al. (1994) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1994.266.1.c172 · Cited by 96 · see citing works
Singer, L. T., Yamashita, T. S., Hawkins, S., et al. (1994) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)81372-1 · Cited by 94 · see citing works
Study of Plasma Factors Associated With Neutrophil Activation and Lipid Peroxidation in Preeclampsia
Barden, A. E., Ritchie, J., Walters, B. N. J., Michael, C., Rivera, J., Mori, T. A., Croft, K. D., & Beilin, L. J. (2001) · Hypertension · doi:10.1161/hy1101.092969 · Cited by 90 · see citing works
Marer, N. L., & Hughes, R. C. (1996) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199607)168:1 · Cited by 84 · 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
Self-citationKarowicz-Bilińska, A., Suzin, J., & Sieroszewski, P. (2002) · PubMed · Cited by 80 · see citing works
The relationship between recent cocaine use and pregnancy outcome.
Mr, S., Williams, R., Digregorio, G. J., et al. (1991) · PubMed · Cited by 67 · see citing works
Kurland, G., Cheung, A., Miller, M. E., et al. (1988) · Pediatric Research · doi:10.1203/00006450-198803000-00013 · Cited by 63 · see citing works
Shen, H., Zhang, Z., Zhang, Q., & Ong, C. N. (2001) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2001.280.1.l10 · Cited by 59 · see citing works
4–Hydroxynonenal Levels Are Enhanced in Fetal Liver Mitochondria By In Utero Ethanol Exposure
Chen, J. J., Schenker, S., & Henderson, G. I. (1997) · Hepatology · doi:10.1002/hep.510250126 · Cited by 58 · see citing works
Bronchoalveolar lavage fluid glutathione in intubated premature infants.
Grigg, J., Barber, A., & Silverman, M. E. (1993) · Archives of Disease in Childhood · doi:10.1136/adc.69.1_spec_no.49 · Cited by 56 · see citing works
Perinatal implications of cocaine exposure.
Burkett, G., Yasin, S. Y., & Palow, D. (1990) · PubMed · Cited by 55 · see citing works
Diedrich, F., Renner, A., Rath, W. H., et al. (2001) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2001.115281 · Cited by 55 · see citing works
Effects of In Utero Administration of Alcohol on Glutathione Levels in Brain and Liver
Reyes, E., Ott, S., & Robinson, B. (1993) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1993.tb00857.x · Cited by 52 · see citing works
Watts, C. L., & Bruce, M. C. (1995) · The Journal of Pediatrics · doi:10.1016/s0022-3476(95)70270-9 · Cited by 51 · see citing works
Abdollah, S., & Brien, J. F. (1995) · Alcohol · doi:10.1016/0741-8329(95)00021-i · Cited by 51 · see citing works
Kimura, K. A., Parr, A. M., & Brien, J. F. (1996) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1996.tb05276.x · Cited by 49 · see citing works
Effects of Chronic Alcohol Abuse on Alveolar Epithelial Barrier Function and Glutathione Homeostasis
Burnham, E. L., Brown, L. A. S., Halls, L., & Moss, M. (2003) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000075821.34270.98 · Cited by 47 · see citing works
Self-citationAddolorato, G., Gasbarrini, A., Marcoccia, S., et al. (1997) · Alcohol · doi:10.1016/s0741-8329(97)00049-9 · Cited by 46 · see citing works
Devi, B. G., Henderson, G. I., Frosto, T. A., et al. (1994) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1994.tb01447.x · Cited by 43 · see citing works
Ethanol Induced Changes in Superoxide Anion and Nitric Oxide in Cultured Microglia
Colton, C. A., Snell‐Callanan, J., & Chernyshev, O. N. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb04315.x · Cited by 41 · see citing works
Glutathione transport by type II cells in perfused rat lung
Bai, C., Brown, L. A. S., & Jones, D. P. (1994) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1994.267.4.l447 · Cited by 36 · see citing works
Self-citationEthanol-induced oxidative stress and enzymatic defenses in cultured fetal rat hepatocytes
Devi, B. G., Schenker, S., Mazloum, B., et al. (1996) · Alcohol · doi:10.1016/0741-8329(96)00002-x · Cited by 34 · see citing works
Kimura, K. A., & Brien, J. F. (1998) · Developmental Brain Research · doi:10.1016/s0165-3806(97)00184-3 · Cited by 34 · see citing works
Oxidative stress and the fetotoxicity of alcohol consumption during pregnancy
Amini, S. A., Dunstan, R. H., Dunkley, P. R., et al. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(96)00027-5 · Cited by 34 · see citing works
Functional immaturity of rat alveolar macrophages during postnatal development
Bakker, J. M., Broug-Holub, E., Kroes, H., van Rees, E. P., Kraal, G., & van Iwaarden, J. F. (1998) · Immunology · doi:10.1046/j.1365-2567.1998.00518.x · Cited by 32 · 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
Glutathione supplements protect preterm rabbits from oxidative lung injury
Brown, L. A. S., Perez, J. A., Harris, F. L., et al. (1996) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1996.270.3.l446 · Cited by 29 · see citing works
Self-citationGuidot, D. M., Moss, M., Holguín, F., et al. (1999) · CHEST Journal · doi:10.1378/chest.116.suppl_1.82s · Cited by 20 · see citing works
In vitro effect of s-adenosyl methionine on ethanol embryopathy in the rat
Seyoum, G., & Persaud, T. V. N. (1994) · Experimental and Toxicologic Pathology · doi:10.1016/s0940-2993(11)80077-1 · Cited by 17 · see citing works
Effects of chronic hepatic dysfunction on pulmonary glutathione homeostasis.
Foreman, M. G., Hoor, T. T., Brown, L. A. S., et al. (2002) · PubMed · doi:10.1097/01.alc.0000042149.71731.b7 · Cited by 17 · see citing works
Self-citationInhibition of neutrophil function by hydrogen peroxide
Rajkovic, I. A., & Williams, R. T. (1985) · Biochemical Pharmacology · doi:10.1016/0006-2952(85)90399-5 · Cited by 16 · see citing works
Developmental aspects of pulmonary defenses in children
Bellanti, J. A., & Zeligs, B. J. (1995) · Pediatric Pulmonology · doi:10.1002/ppul.1950191140 · Cited by 15 · see citing works
Effects of Chronic Hepatic Dysfunction on Pulmonary Glutathione Homeostasis
Foreman, M. G., Hoor, T. T., Brown, L. A. S., et al. (2002) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2002.tb02491.x · Cited by 15 · see citing works
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In utero nicotine exposure promotes M2 activation in neonatal mouse alveolar macrophages
Wongtrakool, C., Grooms, K., Ping, X.-D., Rivera, H., Ward, J., Roser-Page, S., Roman, J., Brown, L. A. S., & Gauthier, T. W. (2012) · Pediatric Research · doi:10.1038/pr.2012.55 · Cited by 31 · see citing works
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- Authors
- Gauthier, T. W., Ping, X.-D., Harris, F. L., Wong, M., Elbahesh, H., & Brown, L. A. S.
- Affiliations
- Emory University (US)
- Corresponding author
- Gauthier, Theresa W
- Venue
- Pediatric Research
- Published
- 2005-01
- Volume
- 57
- Issue
- 1
- Pages
- 76-81
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- OpenAlex
- W2066072238
- Cited by
- 61
- References
- 56
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 6
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r03hd039651-02)
- National Institute on Alcohol Abuse and Alcoholism (R01AA013979)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD39651)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- prenatal alcohol exposure, ethanol, alveolar macrophages, glutathione, oxidative stress, epithelial lining fluid, phagocytosis, macrophage apoptosis, S-adenosylmethionine, glutathione supplementation
- MeSH terms
- Alcohol Drinking, Ethanol, Animals, Cell Survival, Central Nervous System Depressants, Disease Models, Animal, Epithelium, Female, Glutathione, Guinea Pigs, Macrophages, Phagocytosis, S-Adenosylmethionine, Time Factors, Lipid Peroxidation, Apoptosis, Oxidative Stress, Maternal Exposure, In Situ Nick-End Labeling
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