title: Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-alpha and their degranulation is associated with expression of ICAM-1 in the epidermis.
abstract: The release of cytokines from cutaneous cells may be of major importance in the initiation and development of many inflammatory skin disorders. For example, tumor necrosis factor-alpha (TNF-alpha), which in healthy skin is found preformed only in mast cells, is able to induce the expression of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1). Increased expression of ICAM-1 occurs in keratinocytes in lesional skin of psoriasis and atopic dermatitis (AD) and it is considered to be an important initiator of leucocyte/keratinocyte interactions in skin inflammation. We counted the mast cells showing TNF-alpha immunoreactivity using a double-staining method in nonlesional and lesional skin sections from 12 patients with AD and 12 patients with psoriasis. The percentage of TNF-alpha+ mast cells in lesional and nonlesional AD skin was 36 +/- 22% and 21 +/- 15% (P < 0.018, paired t-test), respectively, and in psoriatic skin was 16 +/- 25% and 15 +/- 15%, respectively (P < 0.89, paired t-test). We also cultured whole skin biopsies taken from the healthy-looking skin of psoriatic and AD patients in the presence of mast cell degranulator compound 48/80, which resulted in focal expression of ICAM-1 in the epidermis. In cultured keratinocytes, both histamine and an extract of a human mast-cell line (HMC-1) induced ICAM-1 immunostaining only in occasional cells, but the combination of histamine and the HMC-1 extract resulted in intense ICAM-1 staining in numerous cells. This enhancement of ICAM-1 staining was abolished by preincubation of the HMC-1 extract with anti-TNF-alpha antibody. These results suggest that the degranulation of mast cells induces the expression of ICAM-1 in keratinocytes probably via TNF-alpha and histamine.
authors.affiliation: Department of Dermatology, University of Kuopio, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Ackermann
authors.forename: I T
authors.initials: IT
authors.lastname: Harvima
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001706:Biopsy; D003594:Cytoplasmic Granules / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000378:metabolism* / Q000473:pathology; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000648:ultrastructure; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D006632:Histamine