Archives of Dermatological Research

, Volume 302, Issue 9, pp 685–693 | Cite as

Normal and PPP-affected palmoplantar sweat gland express neuroendocrine markers chromogranins and synaptophysin differently

  • Eva Hagforsen
  • Gerd Michaëlsson
  • Mats Stridsberg
Original Paper


Earlier findings indicate the acrosyringium as the target for the inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat gland apparatus seems to be an immune-competent structure that probably contributes to the defence of the skin. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ because it expresses cholineacetyl-transferase and acetylcholinesterase, nicotinic receptors, beta-adrenergic and angiotensin receptors. The aim of this study was to obtain further information about neuroendocrine properties of the sweat gland apparatus by examining the expression of common neuroendocrine markers synaptophysin and chromogranins A and B in healthy palmar skin and in PPP skin. Synaptophysin and chromogranins were expressed in the sweat glands and ducts with some variation in the pattern and intensity of the expression. In PPP skin the expression differed, being higher and lower, depending on the part of the sweat duct. Chromogranins were further expressed in the epidermis, endothelium and inflammatory cells, but its intensity was weaker in epidermis than in the sweat gland apparatus. In most cases, chromogranins in epidermis in involved PPP were weakly expressed compared to healthy controls. The presence of synaptophysin and chromogranins in palmoplantar skin may have marked neuroendocrine effects, and the palmoplantar skin is likely to have important neuroimmuno-endocrine properties. Moreover, the altered chromogranin expression in PPP skin might influence both the neuroendocrine and neuroimmunologic properties of palmoplantar skin in these patients. These results indicate important neuroendocrine properties of the palmoplantar skin.


Eccrine sweat gland apparatus Neuroendocrine organ Palmoplantar pustulosis Immunohistochemistry Chromogranin 



This study was supported by grants from the Swedish Psoriasis Association, the E Welander and Finsen Foundations, the Swedish Medical Society and the Medical Faculty of the University of Uppsala.

Conflict of interest statement

The authors declare that they have no conflict of interest.


  1. 1.
    Angeletti RH, Hickey WF (1985) A neuroendocrine marker in tissues of the immune system. Science 230:89–90CrossRefPubMedGoogle Scholar
  2. 2.
    Eriksson MO, Hagforsen E, Lundin IP, Michaelsson G (1998) Palmoplantar pustulosis: a clinical and immunohistological study. Br J Dermatol 138:390–398CrossRefPubMedGoogle Scholar
  3. 3.
    Fischer-Colbrie R, Kirchmair R, Kahler CM, Wiedermann CJ, Saria A (2005) Secretoneurin: a new player in angiogenesis and chemotaxis linking nerves, blood vessels and the immune system. Curr Protein Pept Sci 6:373–385CrossRefPubMedGoogle Scholar
  4. 4.
    Galindo E, Rill A, Bader MF, Aunis D (1991) Chromostatin, a 20-amino acid peptide derived from chromogranin A, inhibits chromaffin cell secretion. Proc Natl Acad Sci USA 88:1426–1430CrossRefPubMedGoogle Scholar
  5. 5.
    Hagforsen E (2007) The cutaneous non-neuronal cholinergic system and smoking related dermatoses: studies of the psoriasis variant palmoplantar pustulosis. Life Sci 80:2227–2234CrossRefPubMedGoogle Scholar
  6. 6.
    Hagforsen E, Hedstrand H, Nyberg F, Michaelsson G (2010) Novel findings of Langerhans cells and IL-17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis. Br J Dermatol. doi: 10.1111/j.1365-2133.2010.09819.x
  7. 7.
    Hagforsen E, Michaelsson K, Lundgren E et al (2005) Women with palmoplantar pustulosis have disturbed calcium homeostasis and a high prevalence of diabetes mellitus and psychiatric disorders: a case-control study. Acta Derm Venereol 85:225–232PubMedGoogle Scholar
  8. 8.
    Hagforsen E, Nordlind K, Michaelsson G (2000) Skin nerve fibres and their contacts with mast cells in patients with palmoplantar pustulosis. Arch Dermatol Res 292:269–274CrossRefPubMedGoogle Scholar
  9. 9.
    Hartschuh W, Weihe E, Egner U (1989) Chromogranin A in the mammalian Merkel cell: cellular and subcellular distribution. J Invest Dermatol 93:641–648CrossRefPubMedGoogle Scholar
  10. 10.
    Helle KB (2004) The granin family of uniquely acidic proteins of the diffuse neuroendocrine system: comparative and functional aspects. Biol Rev Camb Philos Soc 79:769–794CrossRefPubMedGoogle Scholar
  11. 11.
    Kahler CM, Schratzberger P, Kaufmann G et al (2002) Transendothelial migration of leukocytes and signalling mechanisms in response to the neuropeptide secretoneurin. Regul Pept 105:35–46CrossRefPubMedGoogle Scholar
  12. 12.
    Kim JE, Cho DH, Kim HS et al (2007) Expression of the corticotropin-releasing hormone-proopiomelanocortin axis in the various clinical types of psoriasis. Exp Dermatol 16:104–109CrossRefPubMedGoogle Scholar
  13. 13.
    Kirchmair R, Hogue-Angeletti R, Gutierrez J, Fischer-Colbrie R, Winkler H (1993) Secretoneurin–a neuropeptide generated in brain, adrenal medulla and other endocrine tissues by proteolytic processing of secretogranin II (chromogranin C). Neuroscience 53:359–365CrossRefPubMedGoogle Scholar
  14. 14.
    Lukinius A, Stridsberg M, Wilander E (2003) Cellular expression and specific intragranular localization of chromogranin A, chromogranin B, and synaptophysin during ontogeny of pancreatic islet cells: an ultrastructural study. Pancreas 27:38–46CrossRefPubMedGoogle Scholar
  15. 15.
    Mahata SK, O’Connor DT, Mahata M et al (1997) Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist. J Clin Invest 100:1623–1633CrossRefPubMedGoogle Scholar
  16. 16.
    Marksteiner J, Kirchmair R, Mahata SK et al (1993) Distribution of secretoneurin, a peptide derived from secretogranin II, in rat brain: an immunocytochemical and radioimmunological study. Neuroscience 54:923–944CrossRefPubMedGoogle Scholar
  17. 17.
    McGregor JM, Barker JN, Allen MH, MacDonald DM (1991) Antigenic profile of human acrosyringium. Br J Dermatol 125:413–418CrossRefPubMedGoogle Scholar
  18. 18.
    Molenaar WM, Lee VM, Trojanowski JQ (1990) Early fetal acquisition of the chromaffin and neuronal immunophenotype by human adrenal medullary cells. An immunohistological study using monoclonal antibodies to chromogranin A, synaptophysin, tyrosine hydroxylase, and neuronal cytoskeletal proteins. Exp Neurol 108:1–9CrossRefPubMedGoogle Scholar
  19. 19.
    Murakami M, Ohtake T, Dorschner RA, Schittek B, Garbe C, Gallo RL (2002) Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin. J Invest Dermatol 119:1090–1095CrossRefPubMedGoogle Scholar
  20. 20.
    Portela-Gomes GM, Stridsberg M (2002) Chromogranin A in the human gastrointestinal tract: an immunocytochemical study with region-specific antibodies. J Histochem Cytochem 50:1487–1492PubMedGoogle Scholar
  21. 21.
    Portela-Gomes GM, Stridsberg M (2002) Region-specific antibodies to chromogranin B display various immunostaining patterns in human endocrine pancreas. J Histochem Cytochem 50:1023–1030PubMedGoogle Scholar
  22. 22.
    Portela-Gomes GM, Stridsberg M (2001) Selective processing of chromogranin A in the different islet cells in human pancreas. J Histochem Cytochem 49:483–490PubMedGoogle Scholar
  23. 23.
    Radek KA, Lopez-Garcia B, Hupe M et al (2008) The neuroendocrine peptide catestatin is a cutaneous antimicrobial and induced in the skin after injury. J Invest Dermatol 128:1525–1534CrossRefPubMedGoogle Scholar
  24. 24.
    Reitamo S, Anttila HS, Didierjean L, Saurat JH (1990) Immunohistochemical identification of interleukin I alpha and beta in human eccrine sweat-gland apparatus. Br J Dermatol 122:315–323CrossRefPubMedGoogle Scholar
  25. 25.
    Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff M (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 86:1309–1379CrossRefPubMedGoogle Scholar
  26. 26.
    Russell J, Gee P, Liu SM, Angeletti RH (1994) Inhibition of parathyroid hormone secretion by amino-terminal chromogranin peptides. Endocrinology 135:337–342CrossRefPubMedGoogle Scholar
  27. 27.
    Schittek B, Hipfel R, Sauer B et al (2001) Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nat Immunol 2:1133–1137CrossRefPubMedGoogle Scholar
  28. 28.
    Slominski A, Wortsman J, Pisarchik A et al (2001) Cutaneous expression of corticotropin-releasing hormone (CRH), urocortin, and CRH receptors. FASEB J 15:1678–1693CrossRefPubMedGoogle Scholar
  29. 29.
    Slominski A, Zbytek B, Zmijewski M et al (2006) Corticotropin releasing hormone and the skin. Front Biosci 11:2230–2248CrossRefPubMedGoogle Scholar
  30. 30.
    Stridsberg M, Lundqvist G, Engstrom U et al (1994) Development of polyclonal antibodies and evaluation of a sensitive radioimmunoassay for detection and measurement of synaptophysin. Acta Neuropathol 87:635–641CrossRefPubMedGoogle Scholar
  31. 31.
    Strub JM, Goumon Y, Lugardon K et al (1996) Antibacterial activity of glycosylated and phosphorylated chromogranin A-derived peptide 173–194 from bovine adrenal medullary chromaffin granules. J Biol Chem 271:28533–28540CrossRefPubMedGoogle Scholar
  32. 32.
    Takeda H, Kondo S (2001) Immunohistochemical study of angiotensin receptors in normal human sweat glands and eccrine poroma. Br J Dermatol 144:1189–1192CrossRefPubMedGoogle Scholar
  33. 33.
    Taupenot L, Harper KL, O’Connor DT (2003) The chromogranin-secretogranin family. N Engl J Med 348:1134–1149CrossRefPubMedGoogle Scholar
  34. 34.
    Wiedenmann B, Franke WW, Kuhn C, Moll R, Gould VE (1986) Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci USA 83:3500–3504CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Eva Hagforsen
    • 1
    • 2
  • Gerd Michaëlsson
    • 1
  • Mats Stridsberg
    • 1
  1. 1.Department of Medical SciencesUniversity of UppsalaUppsalaSweden
  2. 2.Medical Sciences, DermatologyUniversity HospitalUppsalaSweden

Personalised recommendations