Fetal alcohol syndrome (FAS) children have defects in host defense and concomitant increase in the incidence of life threatening infections. Some children with FAS have long lasting deficiencies in both humoral and cell mediated immunity, suggesting that intrauterine exposure to ethanol may interfere with critical events in development of the immune system. Recent studies from this laboratory have shown that in utero exposure to ethanol caused a retarded development of B lymphocytes in neonatal mice. Phenotypic analysis of bone marrow and spleen showed that several intermediates in the B cell development pathway were affected by the fetal ethanol exposure. It addition, we noted that an unknown cell type, with an five weeks of age the splenic B cell population had returned to near normal levels, however, the B cell intermediates in the bone marrow remained below normal values at >5 weeks of age in the fetal ethanol animals. The overall goal of this proposal is to determine the mechanisms by which fetal ethanol exposure uterine exposure to ethanol on B cell developmental intermediates. We will determine the effects of intradiet containing ethanol, to (a) animals whose mothers will be pair fed a control liquid diet and (b) animals whose mothers will fed a stock diet. We will set up timed pregnancies and the dams will be fed the appropriate liquid diet for various periods (13-19 days), which will span the critical period of fetal B cell in these studies will be prepared from fetal liver taken at days 13-19 of gestation, and from bone marrow and spleens of mice 1 day old and then weekly through 6-8 weeks of age. We will determine the absolute of B cell progenitors at different stages of development using flow cytometry and fluorescence microscopy. B cell intermediates will be enriched in cell population by using panning on antibody coated plates and.or sorting by flow cytometry. The colony forming units of the purified progenitors will be determine by measuring the clonal proliferation of the B cell progenitors in soft agar in response to selected growth factors and culture conditions. The developmental potential of the B cell intermediates will be determined by measuring the frequency of cells that can give rise to a more differentiated cell. The long term effects on fetal ethanol will be assessed by testing the immune response of animals of different ages to Type-1 and -2 T independent antigens and to T dependent antigens. Completion of these experiments should provide a thorough understanding of the cellular basis for the effects of alcohol on the differentiation of B cells and suggest potential mechanisms for the clinical immune suppression associated with FAE.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA009876-01
Application #
2046177
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1994-01-01
Project End
1996-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
1
Fiscal Year
1994
Total Cost
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
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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