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CC and CXC chemokines are differentially expressed in erythema multiforme in vivo
Ulrich Spandau1, Eva-Bettina Bröcker, Eckart Kämpgen
1Department of Ophthalmology, University of Würzburg Medical School, Germany. Ulrich.Spandau@augen.ma.uni-heidelberg.de
Background:
A characteristic feature of erythema multiforme is an acute inflammatory reaction of the skin with an infiltrate largely composed of mononuclear cells around the upper dermal vessels and in the dermal-epidermal interface.
Objective:
To determine the composition and localization of leukocyte subsets and corresponding expression of chemokines with chemoattractant properties for lymphocytes and macrophages.
Materials And Methods:
Immunohistochemical analysis was performed to localize leukocyte subsets (CD1(+), CD3(+), CD4(+), CD8(+), and CD68(+)). Expression of transcripts and proteins of chemokines (macrophage chemoattractant protein [MCP] 1); macrophage inflammatory protein [MIP] 1 alpha and MIP-1 beta; regulated on activation, normal T-cell expressed and secreted [RANTES]; growth-related oncogene alpha; epithelial-derived neutrophil attractant 78; interleukin 8; macrophage interferon-gamma inducible gene [Mig]; and interferon-gamma inducible protein 10) was determined by in situ hybridization and immunohistochemical analysis.
Setting:
Department of Dermatology, University of Würzburg Medical School.
Results:
High levels of messenger RNA expression of MCP-1, RANTES, Mig, and interferon-gamma inducible protein 10 were detected and localized in the interface zone and subepidermal infiltrate. In contrast, other investigated chemokines (growth-related oncogene alpha, interleukin 8, epithelial-derived neutrophil attractant 78, I-309, MIP-1 alpha, and MIP-1 beta) were minimally expressed or absent. Protein expression of MCP-1, RANTES, Mig, and interferon-gamma inducible protein 10 was high in the interface zone and low in the subepidermal infiltrate. The messenger RNA expression and protein immunoreactivity patterns overlapped. According to the expression profiles, Mig, interferon-gamma inducible protein 10, MCP-1, and RANTES were expressed by basal keratinocytes above and mononuclear cells within the inflammatory foci.
Conclusion:
These cytokines are important agents in the cytokine network and contribute to the cell-specific and spatially restricted recruitment of mononuclear cells in the acute inflammation of erythema multiforme lesions.