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, 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-alpha positive. A likely explanation for the tissue infiltration of eosinophils could be the release of interleukin-4 and tumor necrosis factor-alpha from activated mast cells. Tumor necrosis factor-alpha 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.
Gijbels
M J
MJ
TNO Prins Maurits Laboratory, Rijsuijk, The Netherlands.
Zurcher
C
C
Kraal
G
G
Elliott
G R
GR
HogenEsch
H
H
Schijff
G
G
Savelkoul
H F
HF
Bruijnzeel
P L
PL
D000818:Animals; D002452:Cell Count; D002455:Cell Division; D002908:Chronic Disease; D003872:Dermatitis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D007073:Immunoglobulin E / Q000032:analysis; D007150:Immunohistochemistry; D007422:Intestines / Q000473:pathology; D008099:Liver / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D012867:Skin / Q000473:pathology; D013154:Spleen / Q000473:pathology
D007073:Immunoglobulin E