title: Delayed neonatal lung macrophage differentiation in a mouse model of in utero ethanol exposure.
abstract: 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.
authors.affiliation: Emory Univ. Dept. of Pediatrics, Division of Neonatal Perinatal Medicine, 2015 Uppergate Dr. NE, Atlanta, GA 30322, USA. tgauthi@emory.edu
authors.forename: Theresa W
authors.initials: TW
authors.lastname: Gauthier
authors.forename: Xiao-Du
authors.initials: XD
authors.lastname: Ping
authors.forename: Levan
authors.initials: L
authors.lastname: Gabelaia
authors.forename: Lou Ann S
authors.initials: LA
authors.lastname: Brown
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D015415:Biomarkers; D002492:Central Nervous System Depressants; D000431:Ethanol
references.citation: Alcohol Clin Exp Res. 2005 Jun;29(6):1035-43
references.pmid: 15976530
references.citation: Life Sci. 2006 Nov 17;79(25):2349-56
references.pmid: 16952379
references.citation: Am Rev Respir Dis. 1993 Nov;148(5):1325-34
references.pmid: 8239171
references.citation: J Leukoc Biol. 1986 Apr;39(4):371-83
references.pmid: 3005455
references.citation: Eur J Pediatr. 1996 Aug;155 Suppl 2:S14-7
references.pmid: 8839740
references.citation: Pediatr Res. 2005 Jan;57(1):76-81
references.pmid: 15531743
references.citation: J Immunol. 1985 Jan;134(1):284-92
references.pmid: 3964815
references.citation: Blood. 1992 Apr 1;79(7):1679-85
references.pmid: 1532754
references.citation: Eur J Immunol. 1996 Aug;26(8):1970-3
references.pmid: 8765047
references.citation: Am J Respir Crit Care Med. 2004 Jul 15;170(2):188-94
references.pmid: 15105163
references.citation: Blood. 1990 Mar 1;75(5):1037-50
references.pmid: 1968349
references.citation: J Immunol. 1995 Aug 1;155(3):1515-24
references.pmid: 7636213
references.citation: J Immunol. 1999 Dec 1;163(11):6164-72
references.pmid: 10570307
references.citation: Pediatr Dev Pathol. 2006 Mar-Apr;9(2):143-51
references.pmid: 16822087
references.citation: J Immunol. 1988 Apr 15;140(8):2645-51
references.pmid: 3258617
references.citation: J Clin Invest. 1998 Feb 15;101(4):890-8
references.pmid: 9466984
references.citation: Am J Respir Crit Care Med. 2005 Jan 1;171(1):73-7
references.pmid: 15466254
references.citation: Semin Neonatol. 2003 Feb;8(1):29-38
references.pmid: 12667828
references.citation: Alcohol. 2004 Jun;33(2):139-45
references.pmid: 15528011
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Nov;285(5):L1132-6
references.pmid: 12896880
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Apr;292(4):L824-32
references.pmid: 17122355
references.citation: J Immunol. 2003 May 1;170(9):4572-7
references.pmid: 12707335
references.citation: Alcohol Clin Exp Res. 2007 Jun;31(6):1031-7
references.pmid: 17403063
references.citation: J Allergy Clin Immunol. 2008 Jun;121(6):1372-8, 1378.e1-3
references.pmid: 18417198
references.citation: J Cell Physiol. 1996 Jul;168(1):26-33
references.pmid: 8647919
references.citation: J Leukoc Biol. 2001 Aug;70(2):163-70
references.pmid: 11493607
references.citation: Alcohol Clin Exp Res. 1995 Feb;19(1):170-6
references.pmid: 7771646
references.citation: Chest. 2004 Feb;125(2):754-65
references.pmid: 14769761
references.citation: Cell Immunol. 2006 Jan;239(1):75-85
references.pmid: 16797505
references.citation: J Reticuloendothel Soc. 1983 Feb;33(2):157-64
references.pmid: 6298414
references.citation: J Immunol. 2002 Dec 1;169(11):6332-42
references.pmid: 12444140
references.citation: Am Rev Respir Dis. 1992 May;145(5):1172-7
references.pmid: 1586063
references.citation: Am J Pathol. 2003 Dec;163(6):2575-84
references.pmid: 14633629
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Aug;281(2):L377-86
references.pmid: 11435212
references.citation: Cell Immunol. 1994 Jun;156(1):191-211
references.pmid: 8200035
references.citation: J Biol Chem. 2000 Jan 14;275(2):1241-6
references.pmid: 10625669
references.citation: J Immunol. 2004 Sep 1;173(5):3398-407
references.pmid: 15322204
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2):L469-75
references.pmid: 17056703
references.citation: J Appl Physiol (1985). 1986 Feb;60(2):353-69
references.pmid: 3005225
references.citation: J Leukoc Biol. 1987 Sep;42(3):188-96
references.pmid: 3497997
references.citation: Alcohol Clin Exp Res. 2007 Feb;31(2):308-16
references.pmid: 17250624
references.citation: J Leukoc Biol. 1994 Feb;55(2):141-6
references.pmid: 8301209
references.citation: J Immunol. 1996 Oct 1;157(7):3097-104
references.pmid: 8816420
references.citation: Pediatr Res. 2004 May;55(5):764-8
references.pmid: 14973182
references.citation: J Lab Clin Med. 1989 Dec;114(6):682-90
references.pmid: 2556490
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Jul;279(1):L25-35
references.pmid: 10893199
references.citation: Pediatrics. 1998 Aug;102(2):e18
references.pmid: 9685463
references.citation: Am J Respir Cell Mol Biol. 2004 Dec;31(6):650-6
references.pmid: 15333328
references.citation: Alcohol Clin Exp Res. 2001 Dec;25(12):1766-72
references.pmid: 11781510
references.citation: Pediatr Pulmonol Suppl. 1995;11:79-80
references.pmid: 7547359
references.citation: Alcohol Clin Exp Res. 2009 Feb;33(2):300-6
references.pmid: 19032578