Modulation of immune function by the brain via the autonomic nervous system requires that neurotransmitters be released from nerves located near their lymphoid target cells, and that these cells recognize and respond to the signal. We have shown that both noradrenergic nerves and peptidergic nerves innervate lymphoid organs and that nerve terminals come in very close contact with lymphocytes and macrophages in specific lymphoid compartments of these organs, providing a local source of neurotransmitter. Our laboratories and others have shown that lymphoid cells have appropriate noradrenergic and peptidergic receptors, and that these neurotransmitters can influence immune function. This project continuation proposes to define further the specificity of contacts between nerve terminals and lymphoid cells, with an emphasis on peptidergic nerves, using immunocytochemical techniques at the light and ultrastructural levels. In addition, we will investigate the possibility of local cytokine feedback from lymphoid cells to these nerve terminals; such feedback may allow lymphoid cell control over their microenvironment during immune responses. We will use in situ hybridization for IL-1 receptor and IL-2 receptor mRNA in the coeliac-superior mesenteric ganglion (the source of efferent innervation to the spleen) to determine whether these neurons can make appropriate receptors, followed by developing antibody probes for immunocytochemical localization of these receptors on nerve terminals in the spleen. Finally, we will use in oculo culture of splenic fragments to gain a refined understanding about the relationship between nerves and lymphoid cells in a model system that allows control over reinnervation of the transplanted fragment. These three approaches will greatly enhance our understanding of the basic biology of local interactions between nerves and lymphoid cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025223-06
Application #
2265504
Study Section
Neurology C Study Section (NEUC)
Project Start
1987-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1995-06-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Rochester
Department
Biology
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Kinney, K S; Felten, S Y; Cohen, N (1996) Sympathetic innervation of the amphibian spleen: developmental studies in Xenopus laevis. Dev Comp Immunol 20:51-9
Kinney, K S; Cohen, N; Felten, S Y (1994) Noradrenergic and peptidergic innervation of the amphibian spleen: comparative studies. Dev Comp Immunol 18:511-21
Felten, S Y; Felten, D L (1994) Neural-immune interactions. Prog Brain Res 100:157-62
Bellinger, D L; Lorton, D; Hamill, R W et al. (1993) Acetylcholinesterase staining and choline acetyltransferase activity in the young adult rat spleen: lack of evidence for cholinergic innervation. Brain Behav Immun 7:191-204
Madden, K S; Ackerman, K D; Livnat, S et al. (1993) Neonatal sympathetic denervation alters development of natural killer (NK) cell activity in F344 rats. Brain Behav Immun 7:344-51
Breneman, S M; Moynihan, J A; Grota, L J et al. (1993) Splenic norepinephrine is decreased in MRL-lpr/lpr mice. Brain Behav Immun 7:135-43
Brenner, G J; Felten, S Y; Felten, D L et al. (1992) Sympathetic nervous system modulation of tumor metastases and host defense mechanisms. J Neuroimmunol 37:191-201
Felten, D L; Felten, S Y; Bellinger, D L et al. (1992) Noradrenergic and peptidergic innervation of secondary lymphoid organs: role in experimental rheumatoid arthritis. Eur J Clin Invest 22 Suppl 1:37-41
Bellinger, D L; Ackerman, K D; Felten, S Y et al. (1992) A longitudinal study of age-related loss of noradrenergic nerves and lymphoid cells in the rat spleen. Exp Neurol 116:295-311
Romano, T A; Felten, S Y; Felten, D L et al. (1991) Neuropeptide-Y innervation of the rat spleen: another potential immunomodulatory neuropeptide. Brain Behav Immun 5:116-31

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