Neuropeptides have been demonstrated to exert a variety of effects upon lymphoid cells. The focus of this proposal is to examine the direct effects of the neuropeptides, Substance P (SP), vasoactive intestinal peptide (VIP), and somatostatin on IgA and IgM responses by gut-associated lymphoreticular tissues (GALT). To address this question, well characterized B tumor cell lines and purified B-cell subpopulations from the GALT will be employed.To meet this objective, the following lines of investigation are proposed.First,the immunoregulatory effects of these neuropeptides on antibody secretion, surface antibody expression, and Class II MHC antigen expression on B-cells will be examined by isotype-specific ELISA and flow cytometry. Second, the B-cell differentiating capabilities of these neuropeptides will be assessedat the cellular and molecular levels (mRNA-cDNA hybridization). Third, the immunoregulatory effects these neuropeptides have in concert with B-cell stimulators (cytokine and/or antigen) on B-cells will be examined at both the cellular and molecular levels using procedures previously mentioned.Fourth, the contribution of these neuropeptides to mucosal immunity will be ascertained by blocking in vivo immune responses to sheep red blood cells (SRBC) by systemic and intraperitoneal administration of anti-neuropeptide monoclonal antibodies or by capsaicin treatment during neonatal life. B-cell immune responsiveness to SRBC will be assessed by direct plaque assay and by isotype-specific ELISPOT. Lastly, changes in B-cell neuropeptide and interleukin receptor levels asa consequence of neuropeptide stimulation will be examined by radiolabeled ligand binding studies of whole cells and by flow cytometry of B-cells stained with fluorochrome-conjugated monoclonal anti-receptor antibodies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA054430-02
Application #
3460231
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1992-03-01
Project End
1997-02-28
Budget Start
1993-03-01
Budget End
1994-02-28
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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van Ginkel, F W; Pascual, D W (1996) Recognition of neurokinin 1 receptor (NK1-R): an antibody to a peptide sequence from the third extracellular region binds to brain NK1-R. J Neuroimmunol 67:49-58
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Van Ginkel, F W; Liu, C; Simecka, J W et al. (1995) Intratracheal gene delivery with adenoviral vector induces elevated systemic IgG and mucosal IgA antibodies to adenovirus and beta-galactosidase. Hum Gene Ther 6:895-903
Pascual, D W; Beagley, K W; Kiyono, H et al. (1995) Substance P promotes Peyer's patch and splenic B cell differentiation. Adv Exp Med Biol 371A:55-9
Wu, S; Pascual, D W; VanCott, J L et al. (1995) Immune responses to novel Escherichia coli and Salmonella typhimurium vectors that express colonization factor antigen I (CFA/I) of enterotoxigenic E. coli in the absence of the CFA/I positive regulator cfaR. Infect Immun 63:4933-8
Pascual, D W; Kiyono, H; McGhee, J R (1994) The enteric nervous and immune systems: interactions for mucosal immunity and inflammation. Immunomethods 5:56-72
Pascual, D W; Pascual, V H; Bost, K L et al. (1993) Nitric oxide mediates immune dysfunction in the spontaneously hypertensive rat. Hypertension 21:185-94
Pascual, D W; Bost, K L; Xu-Amano, J et al. (1992) The cytokine-like action of substance P upon B cell differentiation. Reg Immunol 4:100-4