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Transforming growth factor-beta 1 (TGF beta 1) is a potent inhibitor of epithelial cell proliferation and its effects on growth and differentiation have been extensively characterized in cultured keratinocytes. We used two TGF beta 1-specific polyclonal antibodies (anti-LC and anti-CC) to determine the presence of TGF beta 1 peptide in keratinocytes in sections of normal human skin in situ and in both plaque and nonplaque skin from individuals with psoriasis. In contrast to the differentiation phenotype expressed by keratinocytes in normal epidermis, keratinocytes in the psoriatic plaque exhibit a hyperproliferative/regenerative differentiation phenotype. Anti-TGF beta 1 staining was observed primarily in the epidermis. Anti-LC TGF beta 1 antibody stained nonproliferating, differentiated suprabasal keratinocytes intracellularly in normal skin but did not stain psoriatic plaques from five of seven patients. In contrast, anti-CC TGF beta 1 antibody stained suprabasal keratinocytes extracellularly in psoriatic plaques, but did not stain normal skin. Both anti-LC and anti-CC stained suprabasal keratinocytes intracellularly in nonplaque psoriatic skin. Thus, the conformation or structure of TGF beta 1 and its localization vary in keratinocytes with distinct differentiation phenotypes suggesting that TGF beta 1 is a potential modulator of keratinocyte differentiation in vivo. Selective association of TGF beta 1 with nonproliferating keratinocytes in the suprabasal layers of the epidermis and its exclusion from the proliferating keratinocytes in the basal layer suggest that it may be a physiological regulator of keratinocyte proliferation. In addition, the intracellular localization of TGF beta 1 peptide in both normal and psoriatic keratinocytes suggests that it is constitutively synthesized by epidermal keratinocytes in vivo.

psi-3 is a monoclonal antibody that recognizes a 135,000 molecular weight structural component of maturing keratinocytes in psoriasis (the psi-3 antigen) but fails to bind to any constituent of keratinocytes in normal epidermis. This paper describes the occurrence of the psi-3 antigen in a variety of dermatopathologic conditions using immunoperoxidase (biotin-avidin-peroxidase) and immunofluorescence methods which show excellent concordance. In 35 of 36 specimens of psoriasis vulgaris, psi-3 antibody consistently immunolabels the cytoplasm of keratinocytes above the basal layer. At the edges of psoriatic plaques, psi-3 antibody staining extends for a variable distance into lesion-free epidermis. A similar pattern has been found in a certain number of other conditions described in the paper, including squamous cell carcinoma and condyloma acuminatum, but not Darier's disease, basal cell carcinoma, nor lamellar ichthyosis. In all but one condition, the outermost or basal layer of cells is never stained. The only disease in which the lowermost cell layer is stained is a lichen planus-like lesion. The occurrence of psi-3 antigen cannot be correlated with any histologic feature of psoriasis such as acanthosis, loss of the granular layer, or hyperproliferation. The antigen appears to be a unique keratinocyte constituent which is expressed in certain pathologic conditions and which is not detected by any other histologic or immunophenotyping method. It is a potentially valuable addition to the panel of antibodies available for characterizing epithelial cells.

We have compared the staining patterns of Ulex europeus agglutinin (UEA) I-FITC and Helix pomatia agglutinin (HPA)-FITC on normal and psoriatic epidermis in order to follow the production of the binding sites as a function of maturation. We have further characterized them with respect to solvent extraction and enzyme digestion. The bandlike pattern of membrane staining by UEA I in the upper spinous and granular layer cells of normal epidermis is lost in psoriasis. Instead there is a fainter cytoplasmic staining which is largely sensitive to chloroform/methanol extraction, and thus presumably is glycolipid in nature. Epidermal binding of HPA to normal skin sections is mainly seen in cell membranes. It spares the basal layer and then increases from the suprabasal region to the granular layer. HPA staining in the spinous layer is destroyed by extraction with Triton X-100. In contrast, binding to the membranes of cells in psoriatic epidermis is triton-resistant. The result indicates the production of a component early in the maturation pathway which has no counterpart in normal skin. HPA binding to the spinous cells of symptomless skin from psoriatic patients shows decreased sensitivity to Triton X-100 by comparison with normal. The results are discussed in terms of changes in the pathway of keratinocyte maturation in psoriasis.

We have isolated a murine monoclonal antibody, called psi-3, which immunolabels maturing keratinocytes in psoriatic skin but not in normal epidermis. The staining is cytoplasmic and is not extractable with 1% Triton X-100, which suggests that the psi-3 antigen is a structural component of the keratinocyte. Neither basal cells nor invading inflammatory cells are stained in psoriatic skin and the antigen appears to be associated specifically with maturing and not proliferating keratinocytes. Keratinocytes cultured in vitro from skin from nonpsoriatic individuals display the antigen in a granular pattern in differentiated cells. The antigen is also expressed after tape-stripping of normal skin and, therefore, represents an inducible product of normal keratinocytes. The antigen is destroyed by proteinase K and appears to be a protein. On discontinuous sodium dodecyl sulfate-gel electrophoresis, the antigen has been found to have a molecular weight of 135,000. The psi-3 antigen is interpreted as a new keratinocyte product expressed in psoriasis, culture, wound healing, and certain other pathologic skin conditions. The synthesis of such a new antigen would not be expected if keratinocyte maturation in psoriasis is a truncated version of the normal system and supports the hypothesis that psoriatic keratinocytes are following an alternative pathway. Results using experimental injury suggest that the psoriatic pathway is normally expressed during wound healing.