1. We have discovered that two keratin polypeptides synthesized by involved epidermis of individuals with psoriasis are absent in uninvolved epidermis from individuals with or without psoriasis. We have also discovered that these two keratin polypeptides are synthesized by uninvolved epidermis after it has been removed and placed in organ culture. The molecular weights of these two polypeptides are 56 and 50 kilodaltons. The basis of this rapid synthetic response to """"""""injury"""""""" of normal and uninvolved epidermis will be explored. It is assumed that the rapid synthesis of these two keratin peptides is a response to a natural mediator, possibly a product of arachidonic acid. It should be possible to classify or identify this mediator. It is possible that this mediator is important in many hyperproliferative disorders and it seems very likely that it will be involved in the pathogenesis of psoriasis. The regulation of control of keratin polypeptide synthesis will be examined in human and mouse skin in vivo (mouse), in organ culture (mouse, human) and in cell culture (human). Analogies between keratin peptide synthesis in psoriasis and following exposure of mouse skin to TPA will be explored. 2. The behavior of keratinocytes in culture will be studied with reference to conditions influencing attachment, spreading, locomotion, recognition and stratification. These studies will be focused on material synthesized by keratinocytes and deposited on the surface of tissue culture plastic. Preliminary experiments show that the material is not made by bovine endothelial cells or human fibroblasts in culture. The materials is sensitive to trypsin. It is not collagen type IV or V, fibronectin, or laminin. The plan is to identify the material by labeling with 35S-methionine, 125I, or labeled sugars. Using two-dimensional chromatography, products of tryptic digestion will be compared with tryptic peptides of keratin. If the material is related to keratin, then the specific keratin will be identified. The deposited material will be compared with other keratin attachment or spreading factors such as epibolin and vitronectin.
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