Summary
Sections of human skin were processed according to the indirect immunofluorescence technique with a rabbit antiserum against human protein gene product 9.5 (PGP 9.5). Immunoreactivity was detected in intraepidermal and dermal nerve fibres and cells. The intraepidermal nerves were varicose or smooth with different diameters, running as single processes or branched, straight or bent, projecting in various directions and terminating in the stratum basale, spinosum or granulosum. The density of the intraepidermal nerves varied between the different skin areas investigated. PGP 9.5-containing axons of the lower dermis were found in large bundles. They separated into smaller axon bundles within the upper dermis, entering this portion of the skin perpendicular to the surface. Then they branched into fibres mainly arranged parallel to the epidermal-dermal junctional zone. However, the fibres en route to the epidermis traversed the upper dermis more or less perpendicularly. Furthermore, immunoreactive dermal nerve fibres were found in the Meissner corpuscles, the arrector pili muscles, hair follicles, around the eccrine and apocrine sweat glands and around certain blood vessels. Such fibres were also observed around most subcutaneous blood vessels, sometimes heavily innervating these structures. Numerous weakly-to-strongly PGP 9.5-immunoreactive cells were found both in the epidermis and in the dermis.
Similar content being viewed by others
References
Alvarez FJ, Cervantes C, Blasco I, Villalba R, Martinez-Murillo R, Polak JM, Rodrigo J (1988) Presence of calcitonin generelated peptide (CGRP) and substance P (SP) immunoreactivity in intraepidermal free nerve endings of cat skin. Brain Res 442:391–395
Anderson NG, Anderson NL (1979) Molecular anatomy. Behring Inst Mitt 63:169–210
Arthur RP, Shelley WB (1959) The innervation of human epidermis. J Invest Dermatol 32:397–410
Björklund H, Dalsgaard C-J, Jonsson C-E, Hermansson A (1986) Sensory and autonomic innervation of non-hairy and hairy human skin. An immunohistochemical study. Cell Tissue Res 243:51–57
Bock E (1978) Nervous system specific proteins. J Neurochem 30:7–14
Coons AH (1958) Fluorescent antibody methods. In: Danielli JF (ed) General Cytochemical Methods, Vol 1, Academic Press, New York, pp 399–422
Dalsgaard C-J, Jonsson C-E, Hökfelt T, Cuello AC (1983) Localization of substance P-immunoreactive nerve fibers in the human digital skin. Experientia 39:1018–1020
Dalsgaard C-J, Björklund H, Jonsson C-E, Hermansson A, Dahl D (1984) Distribution of neurofilament-immunoreactive nerve fibers in human skin. Histochemistry 81:111–114
Dalsgaard C-J, Jernbeck J, Stains W, Kjartansson J, Haegerstrand A, Hökfelt T, Brodin E, Cuello AC, Brown JC (1989a) Calcitonin gene-related peptide-like immunoreactivity in nerve fibers in the human skin. Relation to fibers containing substance P-, somatostatin-and vasoactive intestinal polypeptide-like immunoreactivity. Histochemistry 91:35–38
Dalsgaard C-J, Rydh M, Haegerstrand A (1989b) Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies. Histochemistry 92:385–390
Day INM, Thompson RJ (1987) Molecular cloning of cDNA coding for human PGP 9.5 protein. A novel cytoplasmic marker for neurones and neuroendocrine cells. FEBS Lett 210:157–160
Doran JF, Jackson P, Kynoch PAM, Thompson RJ (1983) Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis. J Neurochem 40:1542–1547
Gibbins IL, Wattchow D, Coventry B (1987) Two immunohistochemically identified populations of calcitonin gene-related peptide (CGRP)-immunoreactive axons in human skin. Brain Res 414:143–148
Gulbenkian S, Wharton J, Polak JM (1987) The visualisation of cardiovascular innervation in the guinea pig using an antiserum to protein gene product 9.5 (PGP 9.5). J Auton Nerv Syst 18:235–247
Hamid O, Inyama CO, Rode J, Dhillon AP, Polak JM (1986) PGP 9.5 immunoreactivity in normal, undescended testes and testicular tumours. J Pathol 149:214A
Jackson P, Thompson RJ (1981) The demonstration of new human brain-specific proteins by high-resolution two-dimensional polyacrylamide gel electrophoresis. J Neurol Sci 49:429–438
Johansson O (1985) Morphological characterization of the somatostatin-immunoreactive dendritic skin cells in urticaria pigmentosa patients by computerized image analysis. Scand J Immunol 21:431–439
Johansson O (1987) Pain, motility, neuropeptides, and the human skin: Immunohistochemi al observations. In: Tiengo M, Eccles J, Cuello AC, Ottoson D (eds) Advances in Pain Research and Therapy, Vol 20, Raven Press, New York, pp 31–44
Johansson O, Nordlind K (1984) Immunohistochemical localization of somatostatin-like immunoreactivity in skin lesions from patients with urticaria pigmentosa. Virchows Arch [B] 46:155–164
Johansson O, Vaalasti A (1987) Immunohistochemical evidence for the presence of somatostatin-containing sensory nerve fibres in the human skin. Neurosci Lett 73:225–230
Johansson O, Vaalasti A, Tainio H, Ljungberg A (1988) Immunohistochemical evidence of galanin in sensory nerves of human digital skin. Acta Physiol Scand 132:261–263
Johansson O, Hilliges M, Ståhle-Bäckdahl M (1989a) Intraepidermal neuron-specific enolase (NSE)-immunoreactive nerve fibres: evidence for sprouting in uremic patients on maintenance hemodialysis. Neurosci Lett 99:281–286
Johansson O, Ljungberg A, Han S-W, Vaalasti A (1989b) Evidence for γ-MSH containing nerves and neutrophilic granulocytes in the human skin using indirect immunofluorescence. J Invest Dermatol (in press)
Kruger I, Silverman JD, Mantyh PW, Sternini C, Brecha NC (1989) Peripheral patterns of calcitonin-gene-related peptide general somatic sensory innervation: Cutaneous and deep terminations. J Comp Neurol 280:291–302
Longley BJ, Braverman IM, Edelson RL (1988) Immunology and the skin. Current concepts. In: Milstone LM, Edelson RL (eds) Annals of the New York Academy of Sciences, Vol 548, The New York Academy of Sciences, New York, pp 225–232
Lundberg L-M, Alm P, Wharton J, Polak JM (1988) Protein gene product 9.5 (PGP 9.5). A new neuronal marker visualizing the whole uterine innervation and pregnancy-induced and developmental changes in the guinea pig. Histochemistry 90:9–17
McGeer PL, Eccles JC, McGeer EG (1978) Molecular Neurobiology of the Mammalian Brain. Plenum Press, New York, 644 pp
Moore BW, Perez VJ (1968) Specific acidic proteins of the nervous system. In: Carlson FD (ed) Physiological and Biochemical Aspects of Nervous Integration, Prentice-Hall, Englewood Cliffs, pp 343–359
Munger BL (1965) The intraepidermal innervation of the snout skin of the oppossum. A light and electron microscope study, with observations on the nature of Merkel's Tastzellen. J Cell Biol 26:79–97
Munger BL, Ide C (1988) The structure and function of cutaneous sensory receptors. Arch Histol Cytol 51:1–34
Novotny GEK, Gommert-Novotny E (1988) Intraepidermal nerves in human digital skin. Cell Tissue Res 254:111–117
Osborne N, Neuhoff V (1985) The chemical specificity of cells in the mammalian retina: Immunohistochemical evidence. Funkt Biol Med 4:7–13
Pearse AGE (1969) The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series, and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem 17:303–313
Pearse AGE, Polak JM (1972) The neural crest origin of the endocrine polypeptide cells of the APUD series. In: Taylor S (ed) Endocrinology, Heinemann, London, pp 145–152
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
Schmechel D, Marangos PJ, Brightman M (1978) Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature 276:834–836
Springall DR, Ibrahim NBN, Rode J, Sharpe MS, Bloom SR, Polak JM (1986) Endocrine differentiation of extra-pulmonary small cell carcinoma demonstrated by immunohistochemistry using antibody to PGP 9.5, neuron-specific enolase and the C-flanking peptide of human probombesin. J Pathol 150:151–162
Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J (1983) PGP 9.5 a new marker for vertebrate neurons and neuroendocrine cells. Brain Res 278:224–228
Vaalasti A, Tainio H, Johansson O, Rechardt L (1988) Litht and electron microscopic immunocytochemical demonstration of intraepidermal CGRP-containing nerves in human skin. Skin Pharmacol 1:225–229
Weihe E, Hartschuh W (1988) Multiple peptides in cutaneous nerves: Regulators under physiological conditions and a pathogenetic role in skin disease? Seminars Dermatol 7:284–300
Wharton J, Gulbenkian S, Merighi A, Kuhn DM, Jahn R, Taylor KM, Polak JM (1988) Immunohistochemical and ultrastructural localisation of peptide-containing nerves and myocardial cells in the human atrial appendage. Cell Tissue Res 254:155–166
Williams RA, Rode J, Dhillon AP, Charlton IG, McCartney A (1987) PGP 9.5, S 100 protein and neurone specific enolase in ocular melanomas. J Pathol 152:196A
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wang, L., Hilliges, M., Jernberg, T. et al. Protein gene product 9.5-immunoreactive nerve fibres and cells in human skin. Cell Tissue Res 261, 25–33 (1990). https://doi.org/10.1007/BF00329435
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00329435