The teratogenic potential of alcohol is well known and the offspring of mothers who abuse alcohol have been shown to have a broad spectrum of anomalies that have been termed alcohol related birth defects (ARBD). The manifestation of ARB span from reduced birth weight to the unique constellation of features termed fetal alcohol syndrome (FAS). FAS children are the offspring of chronic alcoholic women. However, clinical studies have shown that even moderate drinking during pregnancy can affect fetal development suggesting that alcohol abuse may be one of the leading causes of birth defects. Most studies of the teratogenic effects of alcohol have focused on the morphological and neurological features of the affected infants. However, recent studies have shown ARBD children to be at high risk of having some degree of immune deficiency and consequent increased incidence and severity of infection. Since the immune system is not fully developed at birth the infant's ability to cope with infection is fragile. Therefore, it is important to identify environmental factors that might delay normal immune development and put infants at risk. Recent studies from this laboratory using a murine model of ARBD have shown that in utero exposure to alcohol caused a retarded development of B lymphocytes in fetal liver and neonatal bone marrow and spleen. Phenotypic analysis of developmental intermediates in the B lineage showed several to be affected by in utero alcohol exposure. In particular, the investigator's observed that a previously unreported B cell precursor was decreased in neonatal marrow and spleens of animals exposed in utero to alcohol. In this proposal the applicants will use a model consisting of fetal alcohol exposed and pair-fed and chow-fed control animals to assess the effects of alcohol on B lymphopoiesis during fetal and neonatal life. They will use multiparameter flow cytometry to ascertain the absolute number of B cell intermediates and the phenotype of these cells within the fetal liver and neonatal bone marrow and spleen. The developmental potential of the B cell intermediates will be determined by sorting B-lineage cells and other hematopoietic precursors and stem cells and using clonal analysis to determine if alcohol exposure alters the frequency of cells that are capable of differentiation. They will also follow fetal alcohol exposed animals in to adulthood to determine if the exposure affected the function of the humoral immune system and the longevity of the effect.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA009876-08
Application #
6488797
Study Section
Special Emphasis Panel (ZRG4-ALTX-2 (01))
Program Officer
Foudin, Laurie L
Project Start
1994-01-01
Project End
2003-12-31
Budget Start
2002-01-01
Budget End
2003-12-31
Support Year
8
Fiscal Year
2002
Total Cost
$218,115
Indirect Cost
Name
Louisiana State University Hsc Shreveport
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Shreveport
State
LA
Country
United States
Zip Code
71103
Wang, Hao; Zhou, Huijuan; Chervenak, Robert et al. (2009) Ethanol exhibits specificity in its effects on differentiation of hematopoietic progenitors. Cell Immunol 255:1-7
Wang, Hao; Zhou, Huijuan; Moscatello, Kim M et al. (2006) In utero exposure to alcohol alters cell fate decisions by hematopoietic progenitors in the bone marrow of offspring mice during neonatal development. Cell Immunol 239:75-85
Biber, K L; Moscatello, K M; Dempsey, D C et al. (1998) Effects of in utero alcohol exposure on B-cell development in the murine fetal liver. Alcohol Clin Exp Res 22:1706-12
Moscatello, K M; Biber, K L; Dempsey, D C et al. (1998) Characterization of a B cell progenitor present in neonatal bone marrow and spleen but not in adult bone marrow and spleen. J Immunol 161:5391-8
Monahan, C M; Padgett, E L; Biber, K L et al. (1997) Dose response to ethanol-containing liquid diets for use in a murine model for studies of biological effects due to ethanol consumption. Alcohol Clin Exp Res 21:1092-9
Wolcott, R M; Jennings, S R; Chervenak, R (1995) In utero exposure to ethanol affects postnatal development of T- and B-lymphocytes, but not natural killer cells. Alcohol Clin Exp Res 19:170-6