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. 1996 Mar;148(3):941–950.

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

M J Gijbels 1, C Zurcher 1, G Kraal 1, G R Elliott 1, H HogenEsch 1, G Schijff 1, H F Savelkoul 1, P L Bruijnzeel 1
PMCID: PMC1861706  PMID: 8774148

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-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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baniyash M., Eshhar Z. Inhibition of IgE binding to mast cells and basophils by monoclonal antibodies to murine IgE. Eur J Immunol. 1984 Sep;14(9):799–807. doi: 10.1002/eji.1830140907. [DOI] [PubMed] [Google Scholar]
  2. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bonnefoy J. Y., Aubry J. P., Gauchat J. F., Graber P., Life P., Flores-Romo L., Mazzei G. Receptors for IgE. Curr Opin Immunol. 1993 Dec;5(6):944–949. doi: 10.1016/0952-7915(93)90110-e. [DOI] [PubMed] [Google Scholar]
  4. Bosse R., Vestweber D. Only simultaneous blocking of the L- and P-selectin completely inhibits neutrophil migration into mouse peritoneum. Eur J Immunol. 1994 Dec;24(12):3019–3024. doi: 10.1002/eji.1830241215. [DOI] [PubMed] [Google Scholar]
  5. Bruijnzeel P. L. Eosinophil tissue mobilization in allergic disorders. Ann N Y Acad Sci. 1994 May 28;725:259–267. doi: 10.1111/j.1749-6632.1994.tb39808.x. [DOI] [PubMed] [Google Scholar]
  6. Coffman R. L., Carty J. A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. J Immunol. 1986 Feb 1;136(3):949–954. [PubMed] [Google Scholar]
  7. Dubois G. R., Bruijnzeel-Koomen C. A., Bruijnzeel P. L. IL-4 induces chemotaxis of blood eosinophils from atopic dermatitis patients, but not from normal individuals. J Invest Dermatol. 1994 Jun;102(6):843–846. doi: 10.1111/1523-1747.ep12382362. [DOI] [PubMed] [Google Scholar]
  8. Dubois G. R., Bruijnzeel P. L. IL-4-induced migration of eosinophils in allergic inflammation. Ann N Y Acad Sci. 1994 May 28;725:268–273. doi: 10.1111/j.1749-6632.1994.tb39809.x. [DOI] [PubMed] [Google Scholar]
  9. Galli S. J. New concepts about the mast cell. N Engl J Med. 1993 Jan 28;328(4):257–265. doi: 10.1056/NEJM199301283280408. [DOI] [PubMed] [Google Scholar]
  10. Galli S. J. New insights into "the riddle of the mast cells": microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab Invest. 1990 Jan;62(1):5–33. [PubMed] [Google Scholar]
  11. Galli S. J., Wershil B. K., Costa J. J., Tsai M. For better or for worse: does stem cell factor importantly regulate mast cell function in pulmonary physiology and pathology? Am J Respir Cell Mol Biol. 1994 Dec;11(6):644–645. doi: 10.1165/ajrcmb.11.6.7524569. [DOI] [PubMed] [Google Scholar]
  12. Gijbels M. J., HogenEsch H., Blauw B., Roholl P., Zurcher C. Ultrastructure of epidermis of mice with chronic proliferative dermatitis. Ultrastruct Pathol. 1995 Mar-Apr;19(2):107–111. doi: 10.3109/01913129509014610. [DOI] [PubMed] [Google Scholar]
  13. Gijbels M. J., HogenEsch H., Bruijnzeel P. L., Elliott G. R., Zurcher C. Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa. J Invest Dermatol. 1995 Dec;105(6):769–773. doi: 10.1111/1523-1747.ep12325599. [DOI] [PubMed] [Google Scholar]
  14. Gordon J. R., Burd P. R., Galli S. J. Mast cells as a source of multifunctional cytokines. Immunol Today. 1990 Dec;11(12):458–464. doi: 10.1016/0167-5699(90)90176-a. [DOI] [PubMed] [Google Scholar]
  15. Gotsch U., Jäger U., Dominis M., Vestweber D. Expression of P-selectin on endothelial cells is upregulated by LPS and TNF-alpha in vivo. Cell Adhes Commun. 1994 Apr;2(1):7–14. doi: 10.3109/15419069409014198. [DOI] [PubMed] [Google Scholar]
  16. HogenEsch H., Gijbels M. J., Offerman E., van Hooft J., van Bekkum D. W., Zurcher C. A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice. Am J Pathol. 1993 Sep;143(3):972–982. [PMC free article] [PubMed] [Google Scholar]
  17. Kapp A., Zeck-Kapp G., Czech W., Schöpf E. The chemokine RANTES is more than a chemoattractant: characterization of its effect on human eosinophil oxidative metabolism and morphology in comparison with IL-5 and GM-CSF. J Invest Dermatol. 1994 Jun;102(6):906–914. doi: 10.1111/1523-1747.ep12383399. [DOI] [PubMed] [Google Scholar]
  18. Leeuwenberg J. F., Van Damme J., Meager T., Jeunhomme T. M., Buurman W. A. Effects of tumor necrosis factor on the interferon-gamma-induced major histocompatibility complex class II antigen expression by human endothelial cells. Eur J Immunol. 1988 Sep;18(9):1469–1472. doi: 10.1002/eji.1830180925. [DOI] [PubMed] [Google Scholar]
  19. Malveaux F. J., Conroy M. C., Adkinson N. F., Jr, Lichtenstein L. M. IgE receptors on human basophils. Relationship to serum IgE concentration. J Clin Invest. 1978 Jul;62(1):176–181. doi: 10.1172/JCI109103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Moser R., Groscurth P., Carballido J. M., Bruijnzeel P. L., Blaser K., Heusser C. H., Fehr J. Interleukin-4 induces tissue eosinophilia in mice: correlation with its in vitro capacity to stimulate the endothelial cell-dependent selective transmigration of human eosinophils. J Lab Clin Med. 1993 Nov;122(5):567–575. [PubMed] [Google Scholar]
  21. Norton C. R., Rumberger J. M., Burns D. K., Wolitzky B. A. Characterization of murine E-selectin expression in vitro using novel anti-mouse E-selectin monoclonal antibodies. Biochem Biophys Res Commun. 1993 Aug 31;195(1):250–258. doi: 10.1006/bbrc.1993.2037. [DOI] [PubMed] [Google Scholar]
  22. Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  23. Schröder J. M., Kameyoshi Y., Christophers E. RANTES, a novel eosinophil-chemotactic cytokine. Ann N Y Acad Sci. 1994 May 28;725:91–103. doi: 10.1111/j.1749-6632.1994.tb39793.x. [DOI] [PubMed] [Google Scholar]
  24. Schumacher J. H., O'Garra A., Shrader B., van Kimmenade A., Bond M. W., Mosmann T. R., Coffman R. L. The characterization of four monoclonal antibodies specific for mouse IL-5 and development of mouse and human IL-5 enzyme-linked immunosorbent. J Immunol. 1988 Sep 1;141(5):1576–1581. [PubMed] [Google Scholar]
  25. Wakita H., Sakamoto T., Tokura Y., Takigawa M. E-selectin and vascular cell adhesion molecule-1 as critical adhesion molecules for infiltration of T lymphocytes and eosinophils in atopic dermatitis. J Cutan Pathol. 1994 Feb;21(1):33–39. doi: 10.1111/j.1600-0560.1994.tb00688.x. [DOI] [PubMed] [Google Scholar]
  26. Wong D. T., Weller P. F., Galli S. J., Elovic A., Rand T. H., Gallagher G. T., Chiang T., Chou M. Y., Matossian K., McBride J. Human eosinophils express transforming growth factor alpha. J Exp Med. 1990 Sep 1;172(3):673–681. doi: 10.1084/jem.172.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. de Vries J. E. Novel fundamental approaches to intervening in IgE-mediated allergic diseases. J Invest Dermatol. 1994 Feb;102(2):141–144. doi: 10.1111/1523-1747.ep12371750. [DOI] [PubMed] [Google Scholar]

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