• Stephensen, Charles Bolt (PI)

Project: Research project

Project Details


Recent epidemiologic studies have shown that children with marginal
vitamin A deficiency (VAD) are at increased risk of developing and dying
from respiratory and enteric infections. The secretory IgA system plays
an important role in protecting against such infections. VAD may
increase susceptibility to mucosal infections by decreasing production of
IgA or impairing its transport across epithelial surfaces. Such defects
would be consistent both with vitamin A's well-characterized role in
stimulating and maintaining the differentiation of mucosal epithelial
cells and with its more recently identified role in regulating antibody
production. For these reasons we propose to examine the effect of
vitamin A on the secretory IgA response in BALB/c mice. Specific Aim 1
will determine if VAD affects the mucosal IgA response and serum IgG
response to intranasal infection with influenza A virus or intranasal
immunization with inactivated virus. The following experiments will be
conducted: (A) The concentration of total and influenza A-specific IgA
and IgG will be measured by ELISA in the (i) saliva, (ii) nasopharyngeal
secretions, (iii) tracheal and bronchopulmonary secretions and (iv) serum
of VAD and control mice. (B) The number of plasma cells producing
influenza A-specific IgA and IgG will be enumerated by ELISPOT in the
respiratory tract and spleen of VAD and control mice. (C) The effect of
VAD on protection against reinfection will be determined by measuring
virus replication (by plaque assay) in the upper and lower respiratory
tract of previously infected or immunized VAD and control mice. Specific
Aim 2 will determine if the transport of polymeric IgA (pIgA) via the
polymeric immunoglobulin receptor (pIgR) is affected by vitamin A status.
The following experiments will be conducted: (A) Hepatocyte-mediated
transport of intravenously administered pIgA into the bile will be
measured in VAD and control mice. (B) Hepatocyte pIgR protein levels will
be measured by western immunoblot analysis and compared between VAD and
control mice. (C) Tissue mRNA levels and the rate of transcription of the
pIgR gene will be measured using the monoclonal-antibody
solution-hybridization (MASH) assay and nuclear run-off assays,
respectively, in VAD and control mice.
Effective start/end date4/1/933/31/97


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)


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