Effects of 6-Hydroxydopamine on the Development of the Immune System in Chickens.

Abstract

ABSTRACT. It has been suggested that the sympathetic nervous system communicates with lymphocytes expressing cell surface receptors for neurotransmitters such as norepinephrine (NE), on the basis of the finding that neurotransmitters modify immune responses in mammalian species. We confirmed that chicken lymphocytes in the brusa of Fabricius, thymus and spleen expressed β-adrenergic receptor (β-AR) mRNA from embryonic day (E) 10 and that intracellular cAMP level was elevated by NE, suggesting that lymphocytes express functional β-AR on their surface at an early embryonal stage. To clarify whether the nervous system is involved in the development of the immune system, the effects of 6-hydroxydopamine (6-OHDA), one of sympathectomizing agents, on chicken lymphocytes was investigated. A single injection of 6-OHDA at a dose of 400 µg into a chicken embryo was carried out at E7 or 14 (as referred to E7 group and E14 group, respectively). NE level and the relative proportion of Bu-1a + , CD4 + and CD8 + cells in the spleen of 3-week-old chickens were not altered by 6-OHDA treatment. However, the proliferative responses and expression of IL-2 mRNA in spleen cells cultured with pokeweed mitogen were reduced in E7 group compared with those of control. Furthermore, in CD8 + spleen cells of E14 group of 3-week-old chickens, the expression of β-AR mRNA and the relative increase of intracellular cAMP stimulated with NE were significantly decreased. These results suggest that the sympathetic nervous system affects the development of the immune system. KEY WORDS: β-adrenergic receptor, cytokine, 6-hydroxydopamine, lymphocyte proliferation, norepinephrine.J. Vet. Med. Sci. 65(1): 35-42, 2003 It has been demonstrated that lymphoid organs, including the thymus, spleen and lymph nodes, are innervated by the sympathetic nervous system [9,45]. Norepinephrine (NE), a signaling molecule of the nervous system, is released from sympathetic nerve terminals and binds to high affinity β-adrenergic receptors (β-AR) that are expressed on various immune cells. β-AR transduce signals from NE to G protein, which in turn activates the adenylate cyclase to produce the second messenger cAMP. Stimulation of β-AR by NE has been reported to be associated with the cytokine production [35,36], cell proliferation [2], and the expression of surface molecules on immune cells [8,11,43].In the chicken, it is also observed that catecholamine modulates immune responses such as antibody responses [6,10], phytohemaglutinin wattle response and lymphocyte migration [31]. Denno et al. [6] showed that in vivo NE administration suppressed IgM-and IgG-PFC and in vitro NE treatment of spleen lymphocytes reduced IgM-PFC. This inhibition of IgM-PFC was blocked by treatment with antagonists to α-and β-receptors, suggesting that there are α-and β-receptor sites on lymphocytes and that catecholamine has a regulatory role in immunoglobulin synthesis.6-Hydroxydopamine (6-OHDA) is a neurotoxin that selectively destroys sympathetic nerve fibers with the catecholamine high a...

Age‐related changes in the avian primary lymphoid organs (thymus and bursa of Fabricius)

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The Role of the Sympathetic Nervous System in the Thymus in Health and Disease

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