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      Plasticity of GAP-43 Innervation of the Spleen during Immune Response in the Mouse

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          The amount and distribution of growth-associated protein (GAP-43)-like immunoreactive nerve fibers in the spleen of normal and immunized BALB/c mice were studied using immunohistochemical methods. A significant increase in the amount, as well as redistribution and morphological changes, of the GAP-43-like immunoreactive nerve fibers occurred in PPD (purified protein derivative from tuberculin) immunized animals. In the control animals, the GAP-43-like immunoreactive nerve fibers were found mainly distributed in association with vascular plexuses, with minor extension into the parenchyma of the inner zone of the periarterial lymph sheath. In the immunized animals, in addition to denser vascular plexuses, more fibers appeared in the outer zone of the periarterial lymph sheath, the marginal zone, and the red pulp, all known to be the sites where immune responding lymphocytes are located. Furthermore, the nerve fibers tended to have more branches and bear richer varicosities. The results suggest that active nerve remolding takes place in the spleen during immune response, which may serve as a mechanism through which the nervous system regulates immune responses.

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          Most cited references 10

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          The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system.

          A combination of the glucose oxidase-diaminobenzidine (DAB) method and the DAB-nickel method can successfully bring out details of immunoreactive structures in immunostained preparations. It is especially beneficial for visualizing fibers and terminals.
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            Involvement of peripheral and central catecholamine systems in neural-immune interactions.

            In this review, we have attempted to delineate the current state of knowledge of the relationships between the immune system and one chemically specific component of the nervous system, the noradrenergic system, both in the brain and the periphery. We have discussed recent work describing the presence of noradrenergic innervation in lymphoid tissues in the major lymphatic organs. Our findings demonstrate clearly that the regions in which lymphocytes (mainly T cells) reside, and through which they recirculate, receive direct sympathetic neural input. The immune system can, therefore, be considered 'hard-wired' to the brain. The evidence for receptors on cells of the immune system capable of receiving signals from the brain is discussed. The significance of this 'hard-wiring' to the function of the immune system is considered, both with regard to the effect of its disruption on immune responses, and to the direct and indirect effects of sympathetic neurotransmitter substances on lymphocytes and their behavior in vitro and in vivo. Finally, our detailed analysis of changes occurring in central noradrenergic pathways as a result of stimulation of the immune system leads to an emerging picture of feedback loops from the immune system to the brain. Such circuits employ endocrine, and probably autonomic, outflow to modulate and regulate immune responses.
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              The growth-associated protein gap-43 appears in dorsal root ganglion cells and in the dorsal horn of the rat spinal cord following peripheral nerve injury


                Author and article information

                S. Karger AG
                April 1998
                10 July 1998
                : 5
                : 1-2
                : 53-60
                a Department of Neuroimmunomodulation, Institute of Neurosciences, The Fourth Military Medical University Xi’an, and b Institute of Basic Medical Sciences, Beijing, PR China
                26326 Neuroimmunomodulation 1998;5:53–60
                © 1998 S. Karger AG, Basel

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                Page count
                Pages: 8
                Original Paper


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