Skip to main content
SpringerLink
Log in

Topical tretinoin increases dermal mast cells, induces epidermal mast cell growth factor (c-kit ligand) and modulates its distribution in hairless mice

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

In previous studies we have noted that mast cells are increased in tretinoin-treated photoaged hairless mouse skin. Because UV radiation is known to increase mast cell numbers, we were interested in whether tretinoin alone would modulate the mast cell population in unirradiated mice. Animals were treated topically with 0.05% tretinoin, 5 days a week, for 2, 4, 6, 8 and 10 weeks. Untreated and vehicle controls were included. Biopsies were processed for light microscopy and stained with toluidine blue. Mast cells in the upper and lower dermis were scored separately under high magnification. After 2 weeks of tretinoin, mast cells in the upper dermis were significantly increased, as indicated by the appearance of small, moderately metachromatically granulated cells near the dermal-epidermal junction. Mast cells in the lower dermis, the site of a granulomatous reaction, were large, densely granular and significantly increased after 6 weeks of treatment. Immunohistochemical evaluation for mast cell growth factor (MGF) revealed a marked increase in keratinocyte cytoplasmic staining by week 2. After 4–6 weeks, membrane-associated or intercellular staining was evident. Cells in the upper dermis also showed membrane reactivity for MGF. By 8–10 weeks, epidermal MGF reactivity had dissipated in the more basal keratinocytes. These findings show that topical tretinoin can induce epidermal MGF along with an associated mast cell hyperplasia. It is suggested that the two populations of dermal mast cells may have different functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kligman LH, Murphy GF (1996) Ultraviolet B radiation increases hairless mouse mast cells in a dose dependent manner and alters distribution of UV induced mast cell growth factor. Photochem Photobiol 63: 123–127

    PubMed  CAS  Google Scholar 

  2. Gordon JR, Burd PR, Galli SJ (1990) Mast cells as a source of multifunctional cytokines. Immunol Today 11: 458–464

    Article  PubMed  CAS  Google Scholar 

  3. Galli SJ (1990) New insights into the “riddle of the mast cells” microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab Invest 62: 5–33

    PubMed  CAS  Google Scholar 

  4. Schwartz E, Cruickshank FA, Mezick JA, Kligman LH (1991) Topical all-trans retinoic acid stimulates collagen synthesis in vivo. J Invest Dermatol 96: 975–978

    Article  PubMed  CAS  Google Scholar 

  5. Schwartz E, Kligman LH (1995) Topical tretinoin increases the tropoelastin and fibronectin content of photoaged hairless mouse skin. J Invest Dermatol 104: 518–522

    Article  PubMed  CAS  Google Scholar 

  6. Kim HJ, Bodgan NJ, D’Agostaro LS, Gold LI, Bryce GF (1992) Effect of topical retinoic acids on the levels of collagen mRNA during repair of UVB-induced dermal damage in the skin of the hairless mouse and the possible role of TGF-β as a mediator. J Invest Dermatol 98: 359–363

    Article  PubMed  CAS  Google Scholar 

  7. Chen S, Kiss I, Tramposch KM (1992) Effects of all-trans retionic acid on UVB-irradiated and non-irradiated hairless mouse skin. J Invest Dermatol 98: 248–254

    Article  PubMed  CAS  Google Scholar 

  8. Chaqour B, Seite S, Coutant K, Fourtanier A, Borel J-P, Bellon G (1995) Chronic UVB and all-trans retinoic acid-induced qualitative and quantitative changes in hairless mouse skin. J Photochem Photobiol B 28: 125–135

    Article  CAS  Google Scholar 

  9. Griffiths CEM, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ (1993) Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). New Engl J Med 329: 530–535

    Article  PubMed  CAS  Google Scholar 

  10. Woodley DT, Zelickson AS, Briggman RA, Hamilton TA, Weiss JS, Ellis CN, Voorhees JJ (1990) Treatment of photoaged skin with topical tretinoin increases epidemal-dermal anchoring fibrils: a preliminary report. JAMA 263: 3057–3059

    Article  PubMed  CAS  Google Scholar 

  11. Schwartz E, Mezick JA, Gendimenico GJ, Kligman LH (1994) In vivo prevention of corticosteroid-induced skin atrophy by tretinoin in the hairless mouse is accompanied by modulation of collagen, glycosaminoglycans and fibronetin. J Invest Dermatol 102: 241–246

    Article  PubMed  CAS  Google Scholar 

  12. Lavker RM, Schechter NM (1985) Cutaneous mast cell depletion results from topical corticosteroid usage. J Immunol 135: 2368–2373

    PubMed  CAS  Google Scholar 

  13. Kligman LH, Murphy GF (1994) Topical tretinoin increases dermal mast cells and induces stem cells factor in hairless mice (abstract). J Invest Dermatol 102: 612

    Google Scholar 

  14. Fleischmajer R, Dessau W, Timpl R, Krieg T, Luderschmidt C, Westner M (1980) Immunofluorescence analysis of collagen, fibronectin and basement membrane protein in scleroderma skin. J Invest Dermatol 75: 270–274

    Article  PubMed  CAS  Google Scholar 

  15. Longley J, Morganroth GS, Tyrell L, Ding TG, Anderson DM, Williams DE, Halaban R (1993) Altered metabolism of mast cell growth factor (c-kit ligand) in cutaneous mastocytosis. New Engl J Med 328: 1302–1307

    Article  PubMed  Google Scholar 

  16. Kligman LH, Murphy GF, Kligman AM (1995) Mast cells respond differentially to ultraviolet radiation and all-trans retiooic acid (abstract). Photochem Photobiol 61S: 21S

    Google Scholar 

  17. Markey AC, Churchill LJ, MacDonald DM (1989) Human cutaneous mast cells—a study of fixative and staining reactions in normal skin. Br J Dermatol 120: 625–631

    Article  PubMed  CAS  Google Scholar 

  18. Michel B, Milner Y, David K (1973) Preservation of tissue-fixed immunoglobins in skin biopsies of patients with lupus erythematosus and bullous diseases. Preliminary report. J Invest Dermatol 59: 449–452

    Article  Google Scholar 

  19. Kitamura T, Tange T, Terasawa T, Chiba S, Kuwaki T, Miyagawa K, Piao Y-F, Miyazano K, Urabe A, Takaku F (1989) Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3 or erythropoietin. J Cell Physiol 140: 323–334

    Article  PubMed  CAS  Google Scholar 

  20. Grabbe J, Welker P, Dippel E, Czarnetski BM (1994) Stem cell factor, a novel cutaneous growth factor for mast cells and melanocytes. Arch Dermatol Res 287: 78–84

    Article  PubMed  CAS  Google Scholar 

  21. Weiss RR, Whitaker-Menezes D, Longley J, Bender J, Murphy GF (1995) Human dermal endothelial cells express membrane associated mast cell growth factor. J Invest Dermatol 104: 101–106

    Article  PubMed  CAS  Google Scholar 

  22. Metcalf D, Nicola NA (1991) Direct proliferative actions of stem cell factor on murine bone marrow cells in vitro: effects of combination with colony-stimulating factors. Proc Natl Acad Sci USA 88: 6239–6243

    Article  PubMed  CAS  Google Scholar 

  23. Galli SJ, Tsai M, Wershul BK (1993) The c-kit receptor, stem cell factor and mast cells. What each is telling us about the others? Am Pathol 142: 965–974

    CAS  Google Scholar 

  24. Valent P (1994) The riddle of the mast cell: kit (CD 117)-lig-and as the missing link? Immunol Today 15: 111–114

    Article  PubMed  CAS  Google Scholar 

  25. Coleman JW, Holliday MR, Kimber I, Zsebo KM, Galli SJ (1993) Regulation of mouse peritoneal mast cell secretory functions by stem cell factor, IL-3 or IL-4. J Immunol 150: 556–562

    PubMed  CAS  Google Scholar 

  26. Kitayama I, Otoyama K, Yokozeki H, Nishioka K (1995) Retinoic acid upregulates c-kit ligand production by murine keratinocytes in vitro and increases cutaneous mast cells in vivo. J Dermatol Sci 9: 27–35

    Article  Google Scholar 

  27. Kligman AM, Kligman LH (1988) The treatment of photoaged skin with topical retinoic acid. Perspect Plast Surg 2: 63–86

    Google Scholar 

  28. Kligman LH, Chen HD, Kligman AM (1984) Topical retinoic acid enhances the repair of ultraviolet damaged connective tisue. Connect Tissue Res 12: 139–150

    PubMed  CAS  Google Scholar 

  29. Ignotz RA, Massague J (1986) Transforming growth factor-β stimulates the expression of fibronectin and collagen and their incorporation into ECM. J Biol Chem 261: 4337–4345

    PubMed  CAS  Google Scholar 

  30. Gordon JR, Galli SJ (1994) Promotion of mouse fibroblast collagen gene expression by mast cells stimulated via the Fc RI. Role for mast cell-derived transforming growth factor β and tumor necrosis factor α. J Exp Med 180: 2027–2037

    Article  PubMed  CAS  Google Scholar 

  31. Thompson HL, Burbelo PD, Gabriel G, Yamada Y, Metcalf DD (1991) Murne mast cells synthesize basement membrane components. A potential role for early fibrosis. J Clin Invest 87: 619–623

    PubMed  CAS  Google Scholar 

  32. Norrby K, Enerback L, Franzel L (1976) Mast cell activation and tissue cell proliferation. Cell Tissue Res 170: 289–303

    Article  PubMed  CAS  Google Scholar 

  33. Levi-Schaffer F, Kupietzky A (1990) Mast cells enhance migration into an in vitro wound. Exp Cell Res 188: 42–49

    Article  PubMed  CAS  Google Scholar 

  34. Trabucchi E, Radaelli E, Marazzi M, Foschi D, Masazzi M, Veronesi AM (1988) The role of the mast cell in wound healing. Int J Tissue React 10: 367–372

    PubMed  CAS  Google Scholar 

  35. Matsuda H, Kitamura Y, (1981) Migration of stromal cells supporting mast-cell differentiation into open wound produced in the skin of mice. Exp Hematol 9: 38–43

    PubMed  CAS  Google Scholar 

  36. Farmoush A, McKenzie IC (1983) Sequential histologic changes and mast cell responses in skin during chemically induced carcinogenesis. J Pathol 12: 300–306

    Google Scholar 

  37. Dabbous MK, Walker R, Heney L, Carter LM, Nicholson GL, Woolley DE (1986) Mast cells and matrix degradation at sites of tumour invasion in rat mammary adenocarcinoma. Br J Cancer 54: 459–465

    PubMed  CAS  Google Scholar 

  38. Bromley M, Fisher WD, Wooley DE (1984) Mast cells at sites of cartilage erosion in the rheumatoid joint. Ann Rheum Dis 43: 76–79

    PubMed  CAS  Google Scholar 

  39. Yoffe JR, Taylor DJ, Woolley D (1985) Mast cells products stimulate collagenase and prostaglandin E production by cultures of adherent rheumatoid synovial cells. Biochem Biophys Res Commun 122: 270–276

    Article  Google Scholar 

  40. Saarinen J, Kalkkinen N, Welgus HG, Kovanen PT (1994) Activation of human interstitial procollagenase through direct cleavage of the Leu83-Thr84 bond by mast cell chymase. J Biol Chem 269: 18134–18140

    PubMed  CAS  Google Scholar 

  41. Gruber BL, Marchese MJ, Susuki K, Schwartz LB, Okada Y, Nagase H, Rammamurthy NS (1982) Synovial procollagenase activation by human mast cell tryptase: dependence upon matrix metalloproteinase 3 activation. J Clin Invest 84: 1657–1662

    Article  Google Scholar 

  42. Havima IT, Horsmanheimo L, Naukharinen A, Horsmanheimo M (1994) Mast cell proteinases and cytokines in skin inflammation. Arch Dermatol Res 287: 61–67

    Article  Google Scholar 

  43. Möller A, Czarnetzki BM (1993) Epidermal cytokines and mast cells. In: Luger T, Schwarz T (eds) Epidermal cytokines. Marcel Dekker, New York, pp 377–394

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, University of Pennsylvania, School of Medicine, Rm. 227 CRB, 415 Curie Blvd., 19104, Philadelphia, PA, USA

    Lorraine H. Kligman & George F. Murphy

Authors
  1. Lorraine H. Kligman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. George F. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kligman, L.H., Murphy, G.F. Topical tretinoin increases dermal mast cells, induces epidermal mast cell growth factor (c-kit ligand) and modulates its distribution in hairless mice. Arch Dermatol Res 288, 537–542 (1996). https://doi.org/10.1007/BF02505251

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02505251

Key words

Search

Navigation