Epicutaneous application of leukotriene B4 induces patterns of tenascin and a heparan sulfate proteoglycan epitope that are typical for psoriatic lesions.
Application of leukotriene B4 (LTB4) to normal human skin induces changes similar to those found in psoriatic skin, and it has proved to be a useful model for studying the pathogenesis and treatment of psoriasis. We studied the expression patterns of molecules that have recently been shown to be altered in lesional psoriatic skin, including the extracellular matrix protein tenascin (TN) and the basement membrane and cell surface-associated heparan sulfate proteoglycans (HSPGs). During 72-h the expression of these markers was studied immunohistochemically and the expression of TN was correlated with epidermal proliferation and influx of inflammatory cells. Following the peak influx of polymorphonuclear leukocytes, a marked increase in TN expression was noted in the papillary dermis 72 h after LTB4 application. The expression patterns of basal membrane-associated epitopes of HSPG remained unaltered, whereas the expression of cell surface-associated HSPG disappeared 72 h after LTB4 application. A significant correlation was found between dermal TN expression and epidermal hyperproliferation, and between TN expression and the presence of dermal T cells. These findings indicate that the model of LTB4-induced acute cutaneous inflammation displays many characteristics of early psoriatic lesions and could serve as a model to study some of the cell biological changes in this disease.
Seyger
M M
MM
Department of Dermatology, University Hospital Nijmegen, The Netherlands.
van Pelt
J P
JP
van den Born
J
J
Latijnhouwers
M A
MA
de Jong
E M
EM
D000279:Administration, Cutaneous; D000328:Adult; D002455:Cell Division / Q000187:drug effects; D017453:Dermatitis, Irritant / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007975:Leukotriene B4 / Q000008:administration & dosage* / Q000502:physiology; D008297:Male; D008954:Models, Biological; D011509:Proteoglycans / Q000378:metabolism*; D011565:Psoriasis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D019063:Tenascin / Q000378:metabolism*
D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007975:Leukotriene B4; D011509:Proteoglycans; D019063:Tenascin