Pathogenesis of skin lesions in mice with chronic proliferative dermatitis (cpdm/cpdm)

Marion J.J. Gijbels, Chris Zurcher, Georg Kraal, Graham R. Elliott, Harm HogenEsch, Gerrit Schijff, Huub F.J. Savelkoul, Piet L.B. Bruijnzeel

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm), showing alopecia, epithelial hyperproliferation, infiltration 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, the epidermal thickness was increased, whereas already at 3 weeks, the bromodeoxyuridine incorporation was increased in the basal keratinocytes. However, already at the age of 1 week, skin, lungs, and lymph nodes were infiltrated by eosinophils although no macroscopic lesions were present. Compared 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 week these mast cells became increasingly IgE positive. In contrast, the mast cells of the control animals remained IgE negative. Mast cells of control and cpdm/cpdm mice were interleukin-4 and tumor necrosis factor-α positive. A likely explanation for the tissue infiltration of eosinophils could be the release of interleukin-4 and tumor necrosis factor-α from activated mast cells. Tumor necrosis factor-α may lead to the expression of E-selectin on endothelial cells, facilitating interleukin-4-mediated eosinophil transendothelial migration. Although various pathogenetic aspects of the cpdm/cpdm mouse need further elucidation, 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 inflammatory skin disease because of the severe epidermal proliferation.

Original languageEnglish (US)
Pages (from-to)941-950
Number of pages10
JournalAmerican Journal of Pathology
Volume148
Issue number3
StatePublished - Mar 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Gijbels, M. J. J., Zurcher, C., Kraal, G., Elliott, G. R., HogenEsch, H., Schijff, G., Savelkoul, H. F. J., & Bruijnzeel, P. L. B. (1996). Pathogenesis of skin lesions in mice with chronic proliferative dermatitis (cpdm/cpdm). American Journal of Pathology, 148(3), 941-950.