Mast cells and vasculature in atopic dermatitis--potential stimulus of neoangiogenesis.
BACKGROUND
Atopic dermatitis skin lesions are characterized by inflammatory changes and epithelial hyperplasia requiring angiogenesis. As mast cells may participate in this process via bidirectional secretion of tissue-damaging enzymes and pro-angiogenic factors, the present study aimed to assess the occurrence and possible function of mast cells in the papillary dermis and in epidermal layers of atopic dermatitis lesions.


METHODS
Semi-thin and serial sections in combination with immunohistochemistry, histochemistry and proliferating cell nuclear antigen (PCNA)-activity assays were used and related to epidermal thickness and targeted gene expression studies.


RESULTS
Mast cells were located in the papillary dermis and migrated through the basal lamina into the epidermis of atopic dermatitis lesions. An increased PCNA-activity in cells of superficial epidermal layers indicated an activation of keratinocytes and stimulation of endothelial growth. Only approximately 30% of the papillary mast cells stained with the tryptase were toluidin-blue-positive, and approximately 80% were chymase positive. A high number of mast cells expressed c-kit. Most papillary and epidermal mast cells were localized close to endothelial cells. Vascular expression of endoglin (CD105) demonstrated neoangiogenic processes. Mast cells stimulation led to the expression of proangiogenic factors. Also, gene expression of tissue-damaging factors such as matrix metalloproteinases was increased.


CONCLUSIONS
These data suggest that in atopic dermatitis, mast cells are abundantly localized close to and within the epidermis where they may stimulate neoangiogenesis. Via the new vessels, inflammatory cells, together with complement components and antibodies, can be transported to the epidermis to aid in the defense against environmental antigens and to maintain chronic inflammation.
Groneberg
D A
DA
Department of Pediatric Pneumology and Immunology, Division of Allergy Research, Charité School of Medicine, Free University and Humboldt University, Berlin, Germany.
Bester
C
C
Grützkau
A
A
Serowka
F
F
Fischer
A
A
Henz
B M
BM
Welker
P
P
D001808:Blood Vessels / Q000473:pathology; D002455:Cell Division; D002460:Cell Line; D003876:Dermatitis, Atopic / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology; D004817:Epidermis / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D008407:Mast Cells / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010641:Phenotype; D012867:Skin / Q000098:blood supply*
D020778:Matrix Metalloproteinase 2