Abstract
• Background: The present study was untertaken in an attempt to broaden the spectrum of known neuronal markers and neuropeptides in the main lacrimal gland of the human by light-microscopic immunohistochemistry. • Methods: Using antisera against the neuronal markers protein gene product (PGP) and S-100 protein (S-100), the distribution of nerve fibers in the human main lacrimal gland was studied. Vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were identified by their specific antisera. • Results: The nerve fibers are distributed throughout the interstice between the glandular tubules. Associations were also found between nerve fibers and both the interlobular ductal system and blood vessels (mainly arterioles). Within the glandular lobules isolated groups of secretory cells stained positive for S-100 protein. Nerve fibers situated in the glandular interstice between the tubules showed predominantly positive immunoreactions for the neuropeptide VIP, while only very few fibers stained positive for CGRP, NPY and the catecholamine marker TH. Nerve fibers associated with interlobular blood vessels were mainly CGRP and NPY positive and stained only very rarely for VIP. The epithelia of interlobular ducts and excretory ducts were associated with CGRP-immunoreactive nerve fibers. • Conclusion: The neuropeptides identified in the lacrimal gland indicate the complexity with which a variety of biologic signals regulate and modulate the lacrimal gland.
Similar content being viewed by others
References
Alexander JH, Lennep EW van, Young JA (1972) Water and electrolyte secretion by the exorbital lacrimal gland of the rat studied by micropuncture and catheterization techniques. Pflügers Arch 337:299–309
Bartek J, Durban EM, Hallowes RC, Taylor-Papadimitriou J (1985) A subclass of luminal epithelial cells in the human mammary gland, defined by antibodies to cytokeratins. J Cell Sci 75:17–33
Beckers HJM, Klooster J, Vrensen GFJM, Lamers WPMA (1991) Ultrastructural identification of trigeminal nerve terminals in the pterygopalatine ganglion of rats: an anterograde tracing and immunohistochemical study. Brain Res 557:22–30
Butler JM, Ruskell GL, Cole DF, Unger WG, Zhang SQ, Blank MA, McGregor GP, Bloom SR (1984) Effects of VIIth (facial) nerve degeneration on vasoactive intestinal polypeptide and substance P levels in ocular and orbital tissues of the rabbit. Exp Eye Res 39:523–532
Cripps MM, Bennett DJ (1992) Proenkephalin Aderivatives in lacrimal gland: occurrence and regulation of lacrimal function. Exp Eye Res 54:829–834
Cripps MM, Patchen-Moor K (1989) Inhibition of stimulated lacrimal secretion by met-enkephalinamide. Am J Physiol 257 (Suppl 20):G151-G156
Daalsgard CJ, Rydh M, Hegerstrand A (1989) Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies. His-tochemistry 92:385–389
Dartt DA (1989) Signal transduction and control of lacrimal gland protein secretion: a review. Curr Eye Res 8:619–636
Dartt DA (1994) Regulation of tear secretion. In: Sullivan DA (ed) Lacrimal gland, tear film, and dry eye syndromes: basic science and clinical relevance. Plenum Press, New York, pp 1–9
Dartt DA, Baker AK, Rose PE, Murphy SA, Ronco LV, Unger MF (1988) Role of cyclic AMP and Ca2+ in potentiation of rat lacrimal gland protein secretion. Invest Ophthalmol Vis Sci 29:1732–1738
Dartt DA, Baker AK, Vaillant C, Rose PE (1984) Vasoactive intestinal polypeptide stimulation of protein secretion from rat lacrimal gland acini. Am J Physiol 247:G502
Dartt DA, Rose PE, Joshi VM, Donowitz M, Sharp GWG (1985) Role of calcium in cholinergic stimulation of lacrimal gland protein secretion. Curr Eye Res 4:475–483
Fahrenkrug J (1993) Transmitter role of vasoactive intestinal peptide. Pharmacol Toxicol 72:354–363
Fox RI, Saito I (1994) Sjogren's syndrome: immunologic and neuroendocrine mechanisms. In: Sullivan DA (ed) Lacrimal gland, tear film, and dry eye syndromes: Basic science and clinical relevance. Plenum Press, New York, pp 609–621
Franklin R, Malaty R, Amirpanahi F, Beuerman R (1989) The role of substance P on Neuro-immune mechanisms in the lacrimal gland. Invest Ophthalmol Vis Sci 30:467
Franzen L, Forsgren S, Gustafsson H, Hendriksson R (1993) Irradiation-induced effects on the innervation of rat salivary glands: Changes in enkephalin- and bombesin-like immunoreactivity in ganglionic cells and intraglan dular nerve fibers. Cell Tissue Res 271:529–536
Frey WH II, Nelson JD, Frick ML, Elde RP (1986) Prolactin immunoreactivity in human tears and lacrimal gland: possible implications for tear production. In: Holly FJ (ed) The preocular tear film in health, disease and contact lens wear. Dry Eye Institute, Lubbock, Tex, pp 798–807
Fujita T (1977) Concept of paraneurons. Arch Histol Jpn [Suppl] 40:1–12
Gibbins IL (1990) Target-related patterns of co-existence of neuropeptide Y, vasoactive intestinal peptide, enkepbalin and substance P in cranial parasympathetic neurons innervating the facial skin and exocrine glands of guinea-pigs. Neuroscience 38:541–560
Haimoto H, Takahashi Y, Koshikawa T, Nagura H, Kato K (1985) Immunohistochemical localization of Y-enolase in normal human tissues other than nervous and neuroendocrine tissues. Lab Invest 52:257–263
Haimoto H, Hosoda S, Kato K (1987) Differential distribution of immunoreactive S100α and S100(3 proteins in normal nonnervous human tissues. Lab Invest 57:489–498
Iadarola MJ, Panula P, Mauane EA, Yank HYT (1985) The opioid octapeptide met-enkepbalin-arg-gly-leu: characterization and distribution in rat spinal cord. Brain Res 330:127–134
Ishida-Yamamoto A, Tohyama M (1989) Calcitonin gene-related-peptide in the nervous tissue. Prog Neurobiol 33:335–386
Johansson O, Lundberg JM (1981) Ultrastructural localization of VIPlike immunoreactivity in large densecore vesicles of cholinergic-type nerve terminals in cat exocrine glands. Neuroscience 6:847–862
Karanth SS, Springdall DR, Kuhn DM, Levene MM, Polak JM (1991) An immunocytochemical study of cutaneous innervation and the distribution of neuropeptides and protein gene product 9.5 in man and commonly employed laboratory animals. Am J Anat 191:369–383
Kivelä T (1992) Antigenic profile of the human lacrimal gland. J Histochem Cytochem 40:629–642
Leblanc GG, Landis SC (1988) Target specificity of neuropeptide Y-immunoreactive cranial parasympathetic neurons. J Neurosci 8:146–155
Lehtosalo JI, Uusitalo H, Mahrberg T, Panula P, Palkama A (1989) Nerve fibers showing immunoreactivities for proenkephalin A-derived peptides in the lacrimal glands of the guinea pig. Graefe's Arch Clin Exp Ophthalmol 227:455–458
Leonhardt H (1990) Histologie, Zytologie und Mikroanatomie des Menschen. Thieme, Stuttgart
Lundberg JM, Änggård A, Fahrenkrug J, Hökfelt T, Mutt V (1980) Vasoactive intestinal polypeptide in cholinergic neurons of exocrine glands: functional significance of coexisting transmitters for vasodilation and secretion. Proc Natl Acad Sci USA 77:1651–1655
Matsumoto Y, Tanabe T, Ueda S, Kawata M (1992) Immunohistochemical and enzymehistochemical studies of peptidergic, aminergic and cholinergic innervation of the lacrimal gland of the monkey (Macaca fuscata). J Anton Nerv Syst 37:207–214
Moore BW (1975) Brain specific protein: S-100 protein, 14-3-2 protein, and glial fibrillary protein. Adv Neurochem 1:137
Nikkinen A, Lehtosalo JI, Uusitalo H, Palkama A, Panula P (1984) The lacrimal glands of the rat and the guinea pig are innervated by nerve fibers containing immunoreactivities for substance P and vasoactive intestinal polypeptide. Histochemistry 81:23–27
Oeschger NS, Amirpanahi F, Malaty R, Franklin R (1989) Regulation of Tcell migration: effect of neuropeptides and cell factors on the binding of T-cells to lacrimal gland epithelial cells. Invest Ophthalmol Vis Sci 30:82
Okami T, Yamamoto A, Takada T, Omori K, Uyama M, Tashiro Y (1992) Ultrastructural localization of Na+, K+-ATPase in the exorbital lacrimal gland of rat. Invest Ophthalmol Vis Sci 33:196–204
Orzalesi N, Riva A, Testa F (1971) Fine structure of human lacrimal gland. I. The normal gland. J Submicrosc Cytol 3:283–296
Rode J, Dhillon AP, Doran JF, Jackson P, Thompson RJ (1985) PGP 9.5, a new marker for human neuroendocrine tumours. Histopathology 9:147–158
Romeis B (1989) Mikroskopische Technik. Urban & Schwarzenberg, Munich
Ruskell GL (1975) Nerve terminals and epithelial cell variety in the human lacrimal gland. Cell Tissue Res 158:121–136
Schulz I, Streb H, Bayerdörffer E, Thévenod F (1985) Stimulus-secretion coupling in exocrine glands: the role of inositol-1,4,5-triphosphate, calcium and cAMP. Curr Eye Res 4:467–473
Seifert P, Spitznas M (1994) Demonstration of nerve fibers in human accessory lacrimal glands. Graefe's Arch Clin Exp Ophthalmol 232:107–114
Sibony PA, Walcott B, McKeon C, Jakobiec FA (1988) Vasoactive intestinal polypeptide and the innervation of the human lacrimal gland. Arch Ophthalmol 106:1085–1088
Singh J, Adeghate E, Burrows S, Howarth FC, Donath T (1994) Protein secretion and the identification of neurotransmitters in the isolated pig lacrimal gland. In: Sullivan DA (ed) Lacrimal gland, tear film, and dry eye syndromes: basic science and clinical relevance. Plenum Press, New York, pp 57–60
Stanisz AM, Befus D, Bienenstock J (1986) Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferation by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen. J Immunol 136:152–156
Tamaki M, Iwanaga T, Takeda M, Adachi I, Sato S, Fujita T (1992) Calcitonin gene-related peptide (CGRP)immunoreactive nerve terminals in the whole mount preparations of the dog urethra. Arch Histol Cytol 55:1–11
Thompson RJ, Doran IF, Jackson P, Dhillon AP, Rode J (1983) PGP 9.5 - a new marker for vertebrate neurons and neuroendocrine cells. Brain Res 278:224–228
Tripathi BJ, Tripathi RC (1990) Evidence for the neuroectodermal origin of the human lacrimal gland. Invest Ophthalmol Visual Sci 31:393–395
Tsukahara S, Tanishima T (1974) Adrenergic and cholinergic innervation of the human lacrimal gland. Jpn J Ophthalmol 18:70–77
Uddman R, Alumets J, Ehinger B, Håkanson R, Lorén I, Sundler F (1980) Vasoactive intestinal peptide nerves in ocular and orbital structures of the cat. Invest Ophthalmol Vis Sci 19:878–885
Vigneswaran N, Wilk CM, Heese A, Hornstein OP, Naumann GOH (1990) Immunohistochemical characterization of epithelial cells in human lacrimal glands. I. Normal major and accessory lacrimal glands. Graefe's Arch Clin Exp Ophthalmol 228:58–64
Walcott B, Sibony PA, Keyser KT (1989) Neuropeptides and the innervation of the avian lacrimal gland. Invest Ophthalmol Vis Sci 30:1666–1674
Weihe E (1990) Neuropeptides in primary afferent neurons. In: Zenker W, Neuhuber WL (eds) The primary afferent neuron. Plenum Press, New York, pp 127–159
Weihe E, Nowak E, Gauweiler B, Stuppi S, Nohr D (1989) Proenkephalin-derivatives are co-messenger candidates in cranial postganglionic parasympathetic neurons: opioid control of exocrine function? Biosciences 75:623–626
Williams RM, Singh J, Sharkey KA (1992) Morphological differences in the innervation and mast cell density of the lacrimal gland in young and aged rats. (Abstract) International Conference on the Lacrimal Gland, Tear Film and Dry Eye Syndromes: Basic Science and Clinical Relevance, 14–17 November, Southhampton Parish, Bermuda
Williams RM, Singh J, Sharkey KA (1994) Innervation and mast cells of the rat lacrimal gland. In: Sullivan DA (ed) Lacrimal gland, tear film, and dry eye syndromes: Basic science and clinical relevance. Plenum Press, New York, pp 67–74
Wilson POG, Barber PC, Hamid QA, Power BF, Dhillon AP, Rode J, Day INM, Thompson RJ, Polak JM (1988) The immunolocalization of protein gene product 9.5 using rabbit polyclonal and mouse monoclonal antibodies. Br J Exp Pathol 69:91–104
Zentel HJ, Weihe E (1991) The neuro-B cell link of peptidergic innervation in the bursa Fabricii. Brain Behav Immun 5:132–147
Author information
Authors and Affiliations
Additional information
Presented in part at the Joint European Research Meetings in Ophthalmology and Vision (JERMOV), 15–19 October 1994, Montpellier, France
Rights and permissions
About this article
Cite this article
Seifert, P., Stuppi, S., Spitznas, M. et al. Differential distribution of neuronal markers and neuropeptides in the human lacrimal gland. Graefe's Arch Clin Exp Ophthalmol 234, 232–240 (1996). https://doi.org/10.1007/BF00430415
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00430415