Percutaneous application of peptidoglycan from Staphylococcus aureus induces eosinophil infiltration in mouse skin.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. The lesioned skin of AD patients shows an increased number of inflammatory cells such as eosinophils, mast cells and mononuclear cells in the dermis and superficial Staphylococcus aureus colonization.


OBJECTIVE
The purpose of this study was to determine the effects of peptidoglycan (PEG) from S. aureus on eosinophil induction in murine skin.


METHODS
PEG was applied to the barrier-disrupted abdominal skin of mice every 5 days. Twenty days later, the number of eosinophils in the abdominal skin was counted. The cytokine response in the skin was investigated by RT-PCR and immunohistological analysis. The regulated-upon activation in normal T cells expressed and secreted (RANTES) production from cultured epidermal cells was measured by ELISA.


RESULTS
The skin of mice treated with PEG showed a significantly increased number of eosinophils compared with that of mice treated with vehicle alone. In addition, application of PEG to the abdominal skin of mice increased the expression of mRNA for RANTES, but not that of mRNA for eotaxin, eotaxin-2 and monocyte chemotactic protein-3 in the skin. Immunohistologic analysis demonstrated that the levels of RANTES transcripts corresponded with those of protein synthesis in the epidermis. In vitro experiments using epidermal Langerhans cells (LCs) and keratinocytes (KCs) showed that RANTES production was induced by LCs but not by KCs stimulated with PEG. Furthermore, an intraperitoneal injection of anti-RANTES antibody neutralized the induction of eosinophils in the skin.


CONCLUSIONS
These results suggest that PEG may have an ability to induce eosinophil infiltration in the skin through RANTES production by LCs, and would explain the role of S. aureus colonization in AD patients.
Matsui
K
K
Department of Immunobiology, Meiji Pharmaceutical University, Tokyo, Japan. kmatsui@my-pharm.ac.jp
Wirotesangthong
M
M
Nishikawa
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D007801:Langerhans Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010457:Peptidoglycan / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013211:Staphylococcus aureus / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D018946:Chemokine CCL5; D010457:Peptidoglycan