Abstract
The peptidergic and noradrenergic innervation of rat and human thymus was investigated by immunohistochemistry at the light and electron microscopical level (avidin-biotin-complex, sucrose-phosphate-glyoxylic-acid, and immunogold techniques). The distribution of noradrenergic neural profiles, and positive immunoreactivity for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and neuropeptide Y (NPY) is described in female rats during ageing, and in human children. In the neonatal rat thymus, the arteries and septa are well supplied by fine varicose nerves. In older animals (2 wk–1 y) the number of septa and blood vessels increase and consequently also the innervation. No nerves were found in the cortex. Apart from the innervation of the septal areas, immunoreactivity for CGRP and TH was present in thymic cells. Except for the young rats (neonatal–14 d), all rats showed CGRP positivity in subcapsular/perivascular epithelial cells (type 1 cells). All rat thymuses also contained a few TH positive cells in the medulla, which could only be confirmed as epithelial cells (type 6 cells) in children. Type 1 cells in the human thymus were not CGRP positive, but as in the rat, there were similar TH positive cells in the medulla. It was concluded that in addition to nerves containing CGRP, noradrenaline or dopamine, epithelial cells also contain these transmitters. They could therefore act on different cells (compared with neural targets) in a paracrine manner.
Keywords: Peptidergic and noradrenergic innervation, epithelial cells
Full Text
The Full Text of this article is available as a PDF (961.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Batanero E., de Leeuw F. E., Jansen G. H., van Wichen D. F., Huber J., Schuurman H. J. The neural and neuro-endocrine component of the human thymus. II. Hormone immunoreactivity. Brain Behav Immun. 1992 Sep;6(3):249–264. doi: 10.1016/0889-1591(92)90047-r. [DOI] [PubMed] [Google Scholar]
- Bellinger D. L., Felten S. Y., Felten D. L. Maintenance of noradrenergic sympathetic innervation in the involuted thymus of the aged Fischer 344 rat. Brain Behav Immun. 1988 Jun;2(2):133–150. doi: 10.1016/0889-1591(88)90014-1. [DOI] [PubMed] [Google Scholar]
- Bulloch K., Hausman J., Radojcic T., Short S. Calcitonin gene-related peptide in the developing and aging thymus. An immunocytochemical study. Ann N Y Acad Sci. 1991;621:218–228. doi: 10.1111/j.1749-6632.1991.tb16981.x. [DOI] [PubMed] [Google Scholar]
- Bulloch K., McEwen B. S., Diwa A., Radojcic T., Hausman J., Baird S. The role of calcitonin gene-related peptide in the mouse thymus revisited. Ann N Y Acad Sci. 1994 Nov 25;741:129–136. doi: 10.1111/j.1749-6632.1994.tb23094.x. [DOI] [PubMed] [Google Scholar]
- Dardenne M., Savino W. Control of thymus physiology by peptidic hormones and neuropeptides. Immunol Today. 1994 Nov;15(11):518–523. doi: 10.1016/0167-5699(94)90207-0. [DOI] [PubMed] [Google Scholar]
- Ericsson A., Geenen V., Robert F., Legros J. J., Vrindts-Gevaert Y., Franchimont P., Brene S., Persson H. Expression of preprotachykinin-A and neuropeptide-Y messenger RNA in the thymus. Mol Endocrinol. 1990 Aug;4(8):1211–1218. doi: 10.1210/mend-4-8-1211. [DOI] [PubMed] [Google Scholar]
- Felten D. L. Direct innervation of lymphoid organs: substrate for neurotransmitter signaling of cells of the immune system. Neuropsychobiology. 1993;28(1-2):110–112. doi: 10.1159/000119011. [DOI] [PubMed] [Google Scholar]
- Felten D. L., Felten S. Y., Carlson S. L., Olschowka J. A., Livnat S. Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol. 1985 Aug;135(2 Suppl):755s–765s. [PubMed] [Google Scholar]
- Geppetti P., Maggi C. A., Zecchi-Orlandini S., Santicioli P., Meli A., Frilli S., Spillantini M. G., Amenta F. Substance P-like immunoreactivity in capsaicin-sensitive structures of the rat thymus. Regul Pept. 1987 Sep;18(5-6):321–329. doi: 10.1016/0167-0115(87)90189-3. [DOI] [PubMed] [Google Scholar]
- Gomariz R. P., Lorenzo M. J., Cacicedo L., Vicente A., Zapata A. G. Demonstration of immunoreactive vasoactive intestinal peptide (IR-VIP) and somatostatin (IR-SOM) in rat thymus. Brain Behav Immun. 1990 Jun;4(2):151–161. doi: 10.1016/0889-1591(90)90017-k. [DOI] [PubMed] [Google Scholar]
- Kendall M. D., Atkinson B. A., Muñoz F. J., de la Riva C., Clarke A. G., von Gaudecker B. The noradrenergic innervation of the rat thymus during pregnancy and in the post partum period. J Anat. 1994 Dec;185(Pt 3):617–625. [PMC free article] [PubMed] [Google Scholar]
- Kendall M. D. Functional anatomy of the thymic microenvironment. J Anat. 1991 Aug;177:1–29. [PMC free article] [PubMed] [Google Scholar]
- Kendall M. D. The morphology of perivascular spaces in the thymus. Thymus. 1989;13(3-4):157–164. [PubMed] [Google Scholar]
- Kendall M. D., al-Shawaf A. A. Innervation of the rat thymus gland. Brain Behav Immun. 1991 Mar;5(1):9–28. doi: 10.1016/0889-1591(91)90004-t. [DOI] [PubMed] [Google Scholar]
- Kurz B., Feindt J., von Gaudecker B., Kranz A., Loppnow H., Mentlein R. Beta-adrenoceptor-mediated effects in rat cultured thymic epithelial cells. Br J Pharmacol. 1997 Apr;120(8):1401–1408. doi: 10.1038/sj.bjp.0701045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurz B., von Gaudecker B., Kranz A., Krisch B., Mentlein R. Calcitonin gene-related peptide and its receptor in the thymus. Peptides. 1995;16(8):1497–1503. doi: 10.1016/0196-9781(95)02042-x. [DOI] [PubMed] [Google Scholar]
- Leposavić G., Mićić M., Ugresić N., Bogojević M., Isaković K. Components of sympathetic innervation of the rat thymus during late fetal and postnatal development: histofluorescence and biochemical study. Sympathetic innervation of the rat thymus. Thymus. 1992 Mar;19(2):77–87. [PubMed] [Google Scholar]
- Lorton D., Bellinger D. L., Felten S. Y., Felten D. L. Substance P innervation of the rat thymus. Peptides. 1990 Nov-Dec;11(6):1269–1275. doi: 10.1016/0196-9781(90)90162-x. [DOI] [PubMed] [Google Scholar]
- Magni F., Bruschi F., Kasti M. The afferent innervation of the thymus gland in the rat. Brain Res. 1987 Oct 27;424(2):379–385. doi: 10.1016/0006-8993(87)91483-1. [DOI] [PubMed] [Google Scholar]
- Micevych P. E., Kruger L. The status of calcitonin gene-related peptide as an effector peptide. Ann N Y Acad Sci. 1992 Jun 30;657:379–396. doi: 10.1111/j.1749-6632.1992.tb22784.x. [DOI] [PubMed] [Google Scholar]
- Mićić M., Leposavić G., Ugresić N. Relationships between monoaminergic and cholinergic innervation of the rat thymus during aging. J Neuroimmunol. 1994 Jan;49(1-2):205–212. doi: 10.1016/0165-5728(94)90197-x. [DOI] [PubMed] [Google Scholar]
- Müller S., Weihe E. Interrelation of peptidergic innervation with mast cells and ED1-positive cells in rat thymus. Brain Behav Immun. 1991 Mar;5(1):55–72. doi: 10.1016/0889-1591(91)90007-w. [DOI] [PubMed] [Google Scholar]
- Nabarra B., Andrianarison I. Thymic reticulum of mice. III. The connective compartment (innervation, vascularisation, fibrous tissues and myoid cells). Tissue Cell. 1995 Jun;27(3):249–261. doi: 10.1016/s0040-8166(95)80045-x. [DOI] [PubMed] [Google Scholar]
- Novotny G. E., Sommerfeld H., Zirbes T. Thymic innervation in the rat: a light and electron microscopical study. J Comp Neurol. 1990 Dec 15;302(3):552–561. doi: 10.1002/cne.903020311. [DOI] [PubMed] [Google Scholar]
- Piantelli M., Maggiano N., Larocca L. M., Ricci R., Ranelletti F. O., Lauriola L., Capelli A. Neuropeptide-immunoreactive cells in human thymus. Brain Behav Immun. 1990 Sep;4(3):189–197. doi: 10.1016/0889-1591(90)90022-i. [DOI] [PubMed] [Google Scholar]
- Proceedings of the anatomical society of great britain and ireland. J Anat. 1996 Feb;188(Pt 1):221–246. [PMC free article] [PubMed] [Google Scholar]
- Ren T., Sagar S. M. Induction of c-fos immunostaining in the rat brain after the systemic administration of nicotine. Brain Res Bull. 1992 Nov;29(5):589–597. doi: 10.1016/0361-9230(92)90127-j. [DOI] [PubMed] [Google Scholar]
- Savino W., Dardenne M. Immune-neuroendocrine interactions. Immunol Today. 1995 Jul;16(7):318–322. doi: 10.1016/0167-5699(95)80144-8. [DOI] [PubMed] [Google Scholar]
- Steel J. H., Gon G., Giaid A., O'Halloran D. J., Emson M. A., Van Noorden S., Ghatei M. A., Jones P. M., Amara S. G., Ishikawa H. Localization of calcitonin gene-related peptide in the rat and human pituitary gland using immunocytochemistry and in situ hybridization. CGRP expression during ontogeny and after endocrine manipulations. Ann N Y Acad Sci. 1992 Jun 30;657:135–154. doi: 10.1111/j.1749-6632.1992.tb22763.x. [DOI] [PubMed] [Google Scholar]
- Sundler F., Håkanson R., Ekblad E., Uddman R., Wahlestedt C. Neuropeptide Y in the peripheral adrenergic and enteric nervous systems. Int Rev Cytol. 1986;102:243–269. doi: 10.1016/s0074-7696(08)61277-2. [DOI] [PubMed] [Google Scholar]
- Torre J. C., Surgeon J. W. A methodological approach to rapid and sensitive monoamine histofluorescence using a modified glyoxylic acid technique: the SPG method. Histochemistry. 1976 Oct 22;49(2):81–93. doi: 10.1007/BF00495672. [DOI] [PubMed] [Google Scholar]
- Umeda Y. Inhibition of immune responses by calcitonin gene-related peptide. Ann N Y Acad Sci. 1992 Jun 30;657:552–554. doi: 10.1111/j.1749-6632.1992.tb22832.x. [DOI] [PubMed] [Google Scholar]
- Von Gaudecker B., Kendall M. D., Ritter M. A. Immuno-electron microscopy of the thymic epithelial microenvironment. Microsc Res Tech. 1997 Aug 1;38(3):237–249. doi: 10.1002/(SICI)1097-0029(19970801)38:3<237::AID-JEMT5>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
- Wang F., Millet I., Bottomly K., Vignery A. Calcitonin gene-related peptide inhibits interleukin 2 production by murine T lymphocytes. J Biol Chem. 1992 Oct 15;267(29):21052–21057. [PubMed] [Google Scholar]
- Weihe E., Müller S., Fink T., Zentel H. J. Tachykinins, calcitonin gene-related peptide and neuropeptide Y in nerves of the mammalian thymus: interactions with mast cells in autonomic and sensory neuroimmunomodulation? Neurosci Lett. 1989 May 22;100(1-3):77–82. doi: 10.1016/0304-3940(89)90663-0. [DOI] [PubMed] [Google Scholar]
- Wharton J., Polak J. M. Neuropeptide tyrosine in the cardiovascular system. Ann N Y Acad Sci. 1990;611:133–144. doi: 10.1111/j.1749-6632.1990.tb48927.x. [DOI] [PubMed] [Google Scholar]
- al-Shawaf A. A., Kendall M. D., Cowen T. Identification of neural profiles containing vasoactive intestinal polypeptide, acetylcholinesterase and catecholamines in the rat thymus. J Anat. 1991 Feb;174:131–143. [PMC free article] [PubMed] [Google Scholar]
- de Leeuw F. E., Jansen G. H., Batanero E., van Wichen D. F., Huber J., Schuurman H. J. The neural and neuro-endocrine component of the human thymus. I. Nerve-like structures. Brain Behav Immun. 1992 Sep;6(3):234–248. doi: 10.1016/0889-1591(92)90046-q. [DOI] [PubMed] [Google Scholar]
- van de Wijngaert F. P., Kendall M. D., Schuurman H. J., Rademakers L. H., Kater L. Heterogeneity of epithelial cells in the human thymus. An ultrastructural study. Cell Tissue Res. 1984;237(2):227–237. doi: 10.1007/BF00217140. [DOI] [PubMed] [Google Scholar]