Human psoriatic skin in organ culture: comparison with normal skin exposed to exogenous growth factors and effects of an antibody to the EGF receptor.
Organ cultures were established from psoriatic lesional skin of 24 different individuals and maintained for 8 days under serum-free, growth-factor-free conditions. Nonlesional skin from 14 of the same individuals and normal skin from another 12 individuals were also maintained in organ culture. At the end of the incubation period, the tissues were fixed in formalin and examined histologically. Lesional skin continued to express features of psoriatic plaque, which included irregularly shaped epithelial cells arranged in a disorganized fashion, and elongation of the rete ridges with a thickening in their lower portion. Abnormal epidermal differentiation and separation of the upper epidermal layers from the lower layers was also a consistent feature. In contrast, nonlesional skin from psoriatic patients exhibited a histological appearance which resembled that of site-matched normal skin. When normal skin was exposed to a growth-factor-enriched culture medium during the 8-day incubation period, it exhibited a histological appearance similar to that of psoriatic skin. In addition to abnormal histological features, the psoriatic skin in organ culture released higher amounts of matrix metalloproteinase-9 (MMP-9; 92-kD gelatinase B/type IV collagenase) into the culture fluid than either nonlesional skin or normal skin. Organ cultures of psoriatic lesional skin from 6 individuals were maintained for 8 days in the presence of an antibody to the human epidermal growth-factor (EGF) receptor. The abnormal histological features of the psoriatic tissue were partially ameliorated in the presence of the antibody. These data suggest that growth factors which act through the EGF receptor help to maintain the psoriatic phenotype in organ culture. They also suggest that organ culture may provide a useful tool with which to elucidate the pathophysiological mechanisms of altered keratinocyte proliferation and differentiation in psoriasis.
Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA. varani@umich.edu
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Varani
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Kang
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Stoll
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JT
Elder
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017364:Collagenases / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism; D009924:Organ Culture Techniques; D010641:Phenotype; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology*; D012867:Skin / Q000033:anatomy & histology* / Q000187:drug effects* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D006133:Growth Substances; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9