THE MELANOCYTE SYSTEM AND KERATINIZATION 419 In psoriasis, which is associated with the absence of organised hydro-. lytic enzyme activity, ATPase cells are virtually absent in the lower layers of the epidermis and those in the upper part of the epidermis are abnormal in that they show weak ATPase activity and are without dendrites. Acid phosphatase and sulphatase have not been demonstrated within dendritic cells although they are profusely scattered throughout the psoriatic epi- dermis. Comparative studies on lower mammals also support the hypothesis that the dendritic cells have an influence on the type of keratin produced by the epidermal cells. (Received: 8th March 1966) REFERENCES (1) Masson, P. in The biology ofrnelanornas 4 15 (1948) (N.Y. Acad. Set.). {2) Jarrett, R. and Riley, P. A. Brit. y. Dermatol. In the press. (3) Fitzpatrick, T. B., Brunet, P. and Kukita, A. in Ellis, R. A. and Montagna, W. (eds.) The biology of hair growth (1958) (Academic Press, New York). (4) Billingham, R. E. and Medawar, P. B. _Phil. Trans. Roy. Soc. London Ser. B. f•l? 151 (1953). (5) Jarreft, A. and Riley, P. A. Brit. J. Dermatol. 79 (1963). (6) Jarrett, A. and Spearman, R. I. C. Histochemistry of the skin: _Psoriasis. (1964) (English Universities Press, London). DISCUSSION DR. L. GOLBER6: A substantial proportion of the population are taking phena- thiazines in one form or another, or are exposed to things like chloroquin and it is now suggested that all new drugs should be screened for their ability to combine with melanin as a protective measure against the possibility of damage to the retina. In the skin we have another situation where there is melanin and the possibility of combination with it we know that molecules of this sort also tend to be selectively accumulated in lysosomes and there would be a tendency for such substances to accumulate in the skin. On numerous occasions there have been clinical descriptions of skin staining developing, say, from the administration of phenathiazine, but to what extent are there minimal degrees of change in skin pigmentation which are not so striking as to draw themselves to the attention of the physician, but yet do affect the shade of the skin ? THE LECTURER: Lysosomes are at the present time one of our interests and much of this work on sulphatases and the other acid hydrolases are in point of fact directed to the lysosomal activity of the skin. There is good reason for believing that the skin hydrolases are actually of lysosomal origin. Although the electromicroscopists have for years stoutly denied that they have been able to detect lysosomes in epidermal cells, they are beginning to change their minds. They have now definitely stated that these bodies are present in high level melanocytes, and more recently a paper has been published in which they have admitted seeing them in the epidermis from cases of atopic eczema, but they still deny having seen them in normal skin. However, I feel sure they must be there, at least in the sense that the lysosome is only a concept of containing active hydrolyric enzymes within protective envelopes. The fact that their pictures do not show the usual correct anatomical size or shape of envelope does not
420 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS necessarily mean they do not exist.* Dr. Riley (in my department) has been engaged in work on skin photosensitivity and has shown that these reactions are probably due to damage to skin lysosomes with the consequent liberation of lysosomal enzymes. If the skin is pretreated with lysosomal stabilizers, such as chlorpromazine, these reactions can be prevented. I think that further work along these lines with lysosome stabilizers will ultimately show that many cutaneous reactions are due to lysosome damage. Chloroquin is, I believe, a lysosome stabilizer, and it has been used clini- cally in dermatology for many years as protection against sunlight. At first it was thought to act by increasing the screening effect of the'keratin'layer. This is possible, but as it is a lysosomal stabilizer' it would be capable of protecting the skin because of this property. DR. I. M. GIBSON: You mentioned Phenergan as a lysosomal stabilizer. I believe it is an antihistamine- is there a long and complex series of reactions involved, or is this simple direct action? THE LECTURER: AS far as I know it is a simple direct action and is an effect of Phenergan in addition to its action as an antihistamine. Dr. Rees, a colleague of mine, has shown that the toxic effects of various liver poisons could be protected against by giving Phenergan and other compounds, such as quinine. He considered that they stabilized the outer cell membrane, and the endoplasmic reticulum. These actions, I think, are quite divorced from any antihistaminic effect. *Since the reading of this paper an article has been published by R. L. Ohlson, J. Invest Dermatol. 46, 431, (1966) in which he has demonstrated acid phosphatase activity to be concentrated within bound structures of human epidermal cells. He suggests that these struc- tures may be lysosomes.
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