PATHOGENESIS OF SKIN-LESIONS IN MICE WITH CHRONIC PROLIFERATIVE DERMATITIS (CPDM CPDM)/

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm), showing alopecia, epithelial hyperproliferation, in filtration by eosinophils and macrophages, and vascular dilatation. To further elucidate its pathogenesis, organs of 1-, 2-, 3-, 4-, 5-, and 6-week-old cpdm/cpdm mice were examined At 4 weeks, tbe epidermal thi ckness was increased, whereas already at 3 weeks, the bromodeoxyuridin e incorporation was increased in the basal keratinocytes. However, alr eady at the age of 1 week, skin, lungs, and lymph nodes were infiltrat ed by eosinophils although no macroscopic lesions were present. Compar ed with control animals, 6-week-old cpdm/cpdm mice had decreased serum IgE levels and increased numbers of mast cells. From the age of 1 wee k these mast cells became increasingly IgE positive. In contrast, the mast cells of tbe control animals remained IgE negative. Mast cells of control and cpdm/cpdm mice were interleukin-4 and tumor necrosis fact or-alpha positive A likely explanation for the tissue infiltration of eosinophils could be the release of interleukin-4 and tumor necrosis f actor-alpha fron activated mast cells. Tumor necrosis factor-alpha may had to the expression of E-selectin on endothelial cells, facilitatin g interleukin-4-mediated eosinophil transendothelial migration. Althou gh various pathogenetic aspects of the cpdm/cpdm mouse need further el ucidation, this model can be a tool to study eosinophil infiltration, leukocyte-endothelial cell interactions, and mast cell proliferation. Furthermore, the cpdm/cpdm mouse can be used to study chronic inflamma tory skin disease because of the severe epidermal proliferation.