Original Article

Journal of Investigative Dermatology (1983) 80, 174–180; doi:10.1111/1523-1747.ep12533424

Effects of Retinoid (Ro 10-9359) on the Plasma Membrane of Keratinocytes in Patients with Psoriasis: A Freeze-Fracture Analysis

Yasuo Kitajima and Shunji Mori

Department of Dermatology, Gifu University School of Medicine, Gifu City, Japan

Received 15 January 1982; Accepted 11 June 1982.

Top

Abstract

Although many thin-section ultrastructural studies have recently been carried out on the effects of retinoids on psoriatic skin, few freeze-fracture studies have been performed. Since keratinocyte membrane disturbances may be involved in psoriasis and since retinoids biochemically affect biologic membranes, we employed a freeze-fracture technique to study the effects of retinoid on the junctional and internal structures of membranes. Lesional and nonlesional skin was biopsied from 5 patients with psoriasis vulgaris before and 3 of them after oral treatment with 50 mg of etretinate (Ro 10-9359) per day for 4 weeks.

The most remarkable finding was the reduction in size of desmosomes-from 0.43 plusminus 0.07 mum to 0.23 plusminus 0.08 mum diameter in spinous cells and 0.35 plusminus 0.03 mum to 0.14 plusminus 0.03 mum in horny cells in lesional skin. Similar results were obtained in nonlesional skin. This reduction in desmosomal size appears to be large enough to produce an extensive exfoliation. It was also of great interest that the intramembranous particle density on the P face (the fracture face of the protoplasmic half-layer) of the spinous cell plasma membranes was 1140 plusminus 57/mum2 in lesional and 429 plusminus 89/mum2 in nonlesional skin before treatment, and 1184 plusminus 93/mum2 and 1179 plusminus 147/mum2 after treatment, respectively, although the lesions were clinically resolved. This may suggest that the agent does not revert the keratinocyte membrane from a psoriatic to a normal state despite clinical improvement. Many openings of pinocytotic (or exocytotic) vesicles were produced on the plasma membranes of keratinocytes. This was associated with the appearance of fine granular substances (so-called mucous-like substances) in the intercellular spaces.

Top

References

  1. Fritsch, P: Oral retinoids in dermatology. Int J Dermatol 1981 20: 314–329,  | PubMed | ChemPort |
  2. Peck, GL: Retinoids in clinical dermatology. Progress in Diseases of The Skin 1981 I: Edited by R. Fleischmajer, New York, Grune & Stratton, pp 227–269,
  3. Elias, PM, Williams, ML: Retinoids, cancer, and the skin. Arch Dermatol 1981 117: 160–180,  | Article | PubMed | ChemPort |
  4. Lotan, R: Effects of vitamin A and its analogues (retinoids) on normal and neoplastic cells. Biochim Biophys Acta 1980 605: 33–91,  | Article | PubMed | ISI | ChemPort |
  5. Madison, K, Tong, PhS, Marcelo, CL, Voorhees, JJ: Ro-10-9359 retinoid inhibits both in vitro epidermal cell proliferation and differentiation. Retinoids, Advances in Basic Research and Therapy 1981 Edited by CE Orfanos, O Braun-Falco, EM Farber, Ch Crupper, MK Polano, R Schuppli. New York, Springer-Verlag, p 161,
  6. King, IA, Tabiowo, A: The dermis is required for the synthesis of extracellular glycosaminoglycans in cultured pig epidermis. Biochim Biophys Acta 1980 632: 234–243,  | PubMed | ChemPort |
  7. King, IA, Tabiowo, A: The effect of all-trans-retinoic acid on the synthesis of epidermal cell-surface-associated carbohydrates. Biochem J 1981 194: 341–350,  | PubMed | ChemPort |
  8. Adamo, S, Luca, LM, Joness, CS, Yuspa, SH: Mode of action of retinoid. Involvement in glycosylation reaction of cultured mouse epidermal cells. J Biol Chem 1979 254: 3279–3287,  | PubMed | ChemPort |
  9. Lotan, R, Dennert, G: Stimulatory effects of vitamin A analogs on induction of cell-mediated cytotoxicity in vivo. Cancer Res 1979 39: 55–58,  | PubMed | ChemPort |
  10. Orfanos, CE, Runne, U: Tissue changes in psoriatic plaques after oral administration of retinoid. Dermatologica 1978 157: 15–25,
  11. Meek, RG, Zaharevitz, D, Chen, RF: Membrane effects of retinoids: possible correlation with toxicity. Arch Biochem Biophys 1981 207: 141–147,  | Article | PubMed | ISI | ChemPort |
  12. Caputo, R, Innocenti, M, Peluchetti, D: Plasma membranes in psoriatic cells; a freeze-fracture study. J Invest Dermatol 1978 71: 245–249,  | Article | PubMed | ISI | ChemPort |
  13. Kitajima, Y, Yanagihara, M, Yaoita, H, Mori, S: Plasma membrane ultrastructure of psoriatic cells as observed by freeze-fracture electron microscopy. J Cutan Pathol 1980 7: 203–204,
  14. Pinto da Silva, D, Branton, D: Membrane splitting in a freeze-etching covalent bound ferritin as a membrane marker. J Cell Biol 1970 45: 649–653,  | Article | PubMed | ChemPort |
  15. Elias, PM, Grayson, S, Caldwell, TM, McNutt, NS: Gap junction proliferation in retinoic acid treated human basal cell carcinoma. Lab Invest 1980 42: 469–474,  | PubMed | ISI | ChemPort |
  16. Elias, PM, Grayson, S, Gross, EG, Peck, GL, McNutt, NS: Influence of topical and systemic retinoids on basal cell carcinoma cell membranes. Cancer 1981 48: 932–938,  | PubMed | ChemPort |
  17. Williams, ML, Elias, PM: Nature of skin fragility in patients receiving retinoids for systemic effect. Arch Dermatol 1981 117: 611–619,  | Article | PubMed | ISI | ChemPort |
  18. Plewig, G, Wolff, HH, Braun-Falco, O: Lokalbehandlung normaler und pathologischer menschlicher Haut mit Vitamin A säure. Arch Klin Exp Dermatol 1971 239: 390–413,  | Article | PubMed | ChemPort |
  19. Cristophers, E, Braun-Falco, O: Stimulation der epidermalen DNS synthese durch Vitamin A säure. Arch Klin Exp Dermatol 1968 232: 427–533,  | PubMed |
  20. Kaidbey, KH, Kligman, AM, Yoshida, H: Effects of intensive application of retinoic acid on human skin. Br J Dermatol 1975 92: 639–701,
  21. Kenerva, L, Lauharanta, J, Niemi, K-M, Lassus, A: Fine structure of the intercellular space of psoriatic epidermis during retinoid (Ro 10-9359) and retinoid-PUVA treatment. Acta Dermvenereol (Stockh) 1981 61: 319–328,
  22. Barnett, ML, Szabo, G: Effect of vitamin A on epithelial morphogenesis in vitro. Exp Cell Res 1973 76: 118–126,  | Article | PubMed | ISI | ChemPort |
  23. Peck, GL, Elias, PM, Wetzel, B: Effects of retinoic acid on embryonic chick skin. J Invest Dermatol 1977 69: 463–476,  | Article | PubMed | ChemPort |
  24. Hardy, MM, Sweeny, PR, Bellows, CG: The effects of vitamin A on the fetal mouse in organ culture-an ultrastructure study. J Ultrastruct Res 1978 64: 246–260,  | Article | PubMed | ChemPort |
  25. Elias, PM, McNutt, NS, Friend, DS: Membrane alterations during cornification of mammalian squamous epithelia: a freeze-fraeture, tracer, and thin-section study. Anal Rec 1977 189: 577–593,  | Article | ChemPort |
  26. Caputo, R, Peluchetti, D: The junctions of normal human epidermis:a freeze-fracture study. J Ultrastruct Res 1977 61: 44–61,  | Article | PubMed | ISI | ChemPort |
  27. Kitajima, Y, Mori, S: Plasma membrane ultrastructure of human skin keratinocytes as observed by freeze-fracture electron microscopy. J Dermatol (Tokyo) 1979 6: 153–160,  | ChemPort |
  28. Kitajima, Y, Maeda, M, Mori, S: Alterations of desmosomal particle architecture associated with keratinization; an observation of human keratinocytes by freeze-fracture electron microscopy. J Clin Elec Microscopy 1979 12: 5–6,
  29. Tagami, M, Ofuji, S: Leucotactic properties of soluble substances in psoriasis scale. Br J Dermatol 1976 95: 1–8,  | PubMed | ChemPort |
  30. Tagami, M, Ofuji, S: Characterization of a leucotactic factor derived from psoriatic scale. Br J Dermatol 1977 97: 509–518,  | PubMed | ChemPort |

Extra navigation

.
ADVERTISEMENT