In Vivo Dysfunction of the Term Alveolar Macrophage After in Utero Ethanol Exposure

Ping, Xiao-Du; Harris, Frank L.; Brown, Lou Ann S.; Gauthier, Theresa W.

doi:10.1111/j.1530-0277.2006.00306.x

Cited by 39 publications

(50 citation statements)

References 66 publications

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“…For some pregnant dams, Sadenosylmethionine (SAM-e, 10 mM, Nature Made) was added to the experimental liquid diet beginning E2. Maternal SAM-e was chosen, as we have demonstrated that it maintains neonatal AM function despite in utero ETOH exposure at both premature and term gestations in the guinea pig model (19,20,35). The females were pair fed to match the ETOH-exposed dam.…”

Section: Methodsmentioning

confidence: 99%

“…To quantify the phagocytosis of FITC-S. aureus by the isolated AM and IM, confocal fluorescent microscopy was used as previously described by this laboratory (8,35). After incubation, the cells were washed and then fixed with 3.7% paraformaldehyde and nonspecific binding blocked with BSA.…”

Section: Differentiation Markers Of Im and Ammentioning

confidence: 99%

“…Limited clinical studies suggest that both term (17) and premature newborns (18) are at increased risk of sepsis after in utero alcohol exposure. Our laboratory has demonstrated in a guinea pig model of in utero ethanol (ETOH) exposure that ETOH increased oxidant stress in the developing lung and within the resident neonatal AM, deranging neonatal AM function both in vitro (19) and in vivo (35) and increasing the risk of experimental pneumonia (20). The capacity of precursors of the antioxidant glutathione (GSH) to modulate these changes in both premature and term gestations demonstrated that exaggerated oxidant stress was a central feature in the dysfunction of the ETOH-exposed developing AM (19,20,35).…”

mentioning

confidence: 99%

“…Our laboratory has demonstrated in a guinea pig model of in utero ethanol (ETOH) exposure that ETOH increased oxidant stress in the developing lung and within the resident neonatal AM, deranging neonatal AM function both in vitro (19) and in vivo (35) and increasing the risk of experimental pneumonia (20). The capacity of precursors of the antioxidant glutathione (GSH) to modulate these changes in both premature and term gestations demonstrated that exaggerated oxidant stress was a central feature in the dysfunction of the ETOH-exposed developing AM (19,20,35).In the adult lung, transforming growth factor-␤ 1 (TGF-␤ 1 ) plays a crucial role in lung injury and repair (2). Chronic ETOH ingestion increases TGF-␤ 1 within the adult lung, primarily in AM and alveolar epithelial type II cells, increasing the risk of cellular dysfunction in the lung (3).…”

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confidence: 99%

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Delayed neonatal lung macrophage differentiation in a mouse model of in utero ethanol exposure

Gauthier

Ping

Gabelaia

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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We have previously demonstrated that fetal ethanol exposure deranges the function and viability of the neonatal alveolar macrophage. Although altered differentiation of the alveolar macrophage contributes to pulmonary disease states within the adult lung, the effects of fetal ethanol exposure on the normal differentiation of interstitial to alveolar macrophage in the newborn lung are unknown. In the current study, using a mouse model of fetal ethanol exposure, we hypothesized that altered terminal differentiation of the neonatal interstitial to alveolar macrophage contributes to the observed cellular dysfunction in the ethanol-exposed newborn mouse. Control alveolar macrophage differentiation was characterized by increased expression of CD32/CD11b (P < or = 0.05) and increased in vitro phagocytosis of Staphylococcus aureus (P < or = 0.05) compared with interstitial macrophage. After in utero ethanol exposure, both alveolar and interstitial macrophage lacked the acquisition of CD32/CD11b (P < or = 0.05) and displayed impaired in vitro phagocytosis (P < or = 0.05). Ethanol significantly increased transforming growth factor-beta(1) (TGF-beta(1)) in the bronchoalveolar lavage fluid (P < or = 0.05), as well as in both interstitial and alveolar macrophages (P < or = 0.05). Oxidant stress contributed to the ethanol-induced changes on the interstitial and alveolar cells, since maternal supplementation with the glutathione precursor S-adenosylmethionine during ethanol ingestion normalized CD32/CD11b (P < or = 0.05), phagocytosis (P < or = 0.05), and TGF-beta(1) in the bronchoalveolar lavage fluid and macrophages (P < or = 0.05). Contrary to our hypothesis, fetal ethanol exposure did not solely impair interstitial to alveolar macrophage differentiation. Rather, fetal ethanol exposure impaired both neonatal interstitial and alveolar macrophage phagocytic function and differentiation. Increased oxidant stress and elevated TGF-beta(1) contributed to the impaired differentiation of both interstitial and alveolar macrophage.

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Section: Methodsmentioning

confidence: 99%

Section: Differentiation Markers Of Im and Ammentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Delayed neonatal lung macrophage differentiation in a mouse model of in utero ethanol exposure

Gauthier

Ping

Gabelaia

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In particular, numerous examples of misregulated function involving myelomonocytic-derived cells were seen following prenatal-neonatal exposures to toxicants or after certain maternal infections (Miller et al, 1998;Chen et al, 1999;Wierzba-Bobrowicz et al, 2003;Mainali et al, 2005;Pace et al, 2005;Ping et al, 2007). Additionally, environmental interference with T-cell selection during thymus maturation and/or with T regulatory cells (Tregs) increases the risk of postnatal autoimmunity.…”

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confidence: 97%

Potential for Early-Life Immune Insult Including Developmental Immunotoxicity in Autism and Autism Spectrum Disorders: Focus on Critical Windows of Immune Vulnerability

Dietert

Dietert²

2008

Journal of Toxicology and Environmental Health, Part B

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Early-life immune insults (ELII) including xenobiotic-induced developmental immunotoxicity (DIT) are important factors in childhood and adult chronic diseases. However, prenatal and perinatal environmentally induced immune alterations have yet to be considered in depth in the context of autism and autism spectrum disorders (ASDs). Numerous factors produce early-life-induced immune dysfunction in offspring, including exposure to xenobiotics, maternal infections, and other prenatal-neonatal stressors. Early life sensitivity to ELII, including DIT, results from the heightened vulnerability of the developing immune system to disruption and the serious nature of the adverse outcomes arising after disruption of one-time immune maturational events. The resulting health risks extend beyond infectious diseases, cancer, allergy, and autoimmunity to include pathologies of the neurological, reproductive, and endocrine systems. Because these changes may include misregulation of resident inflammatory myelomonocytic cells in tissues such as the brain, they are a potential concern in cases of prenatal-neonatal brain pathologies and neurobehavioral deficits. Autism and ASDs are chronic developmental neurobehavioral disorders that are on the rise in the United States with prenatal and perinatal environmental factors suspected as contributors to this increase. Evidence for an association between environmentally associated childhood immune dysfunction and ASDs suggests that ELII and DIT may contribute to these conditions. However, it is not known if this linkage is directly associated with the brain pathologies or represents a separate (or secondary) outcome. This review considers the known features of ELII and DIT and how they may provide important clues to prenatal brain inflammation and the risk of autism and ASDs.

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Developmental Immunotoxicology

Dietert

2009

General, Applied and Systems Toxicology

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Developmental immunotoxicology (DIT) is the study of the impact of chemicals, drugs, physical factors and other agents on the immune system of the nonadult (prenatal, neonatal and juvenile). To achieve complete maturation and full competence, the immune system undergoes a series of novel maturational events during critical windows of development. These events lack exact equivalents in the adult. Not surprisingly, disruption of these early‐life events can have profound and persistent adverse consequences impacting the health and wellbeing of the affected child or adult. Because the developing immune system has been shown to be more sensitive to environmentally induced disruption than is the fully matured immune system of an adult, determination or of immuntoxic risk for the non adult is a growing concern. A dysfunctional immune system appears to be linked to many of the most prevalent chronic diseases of children and adults. For this reason, improved DIT safety testing and resulting immunotoxicity‐associated risk reduction, could have a significant health benefit. This chapter describes: (i) the windows of vulnerability for the developing immune system, (ii) toxicants reported to disrupt immune development, (iii) the importance of gender in risk of developmental immunotoxicity, (iv) the nature of the adverse health outcomes resulting from developmental immunotoxicity and (v) approaches to developmental immunotoxicity safety testing.

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In Vivo Dysfunction of the Term Alveolar Macrophage After in Utero Ethanol Exposure

Cited by 39 publications

References 66 publications

Delayed neonatal lung macrophage differentiation in a mouse model of in utero ethanol exposure

Delayed neonatal lung macrophage differentiation in a mouse model of in utero ethanol exposure

Potential for Early-Life Immune Insult Including Developmental Immunotoxicity in Autism and Autism Spectrum Disorders: Focus on Critical Windows of Immune Vulnerability

Developmental Immunotoxicology

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