Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1.
Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that mediates endothelial leukocyte interactions by inducing expression of adhesion molecules. In this report, we demonstrate that human dermal mast cells contain sizeable stores of immunoreactive and biologically active TNF-alpha within granules, which can be released rapidly into the extracellular space upon degranulation. Among normal human dermal cells, mast cells are the predominant cell type that expresses both TNF-alpha protein and TNF-alpha mRNA. Moreover, induction of endothelial leukocyte adhesion molecule 1 expression is a direct consequence of release of mast cell-derived TNF-alpha. These findings establish a role for human mast cells as "gatekeepers" of the dermal microvasculature and indicate that mast cell products other than vasoactive amines influence endothelium in a proinflammatory fashion.
Walsh
L J
LJ
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Trinchieri
G
G
Waldorf
H A
HA
Whitaker
D
D
Murphy
G F
GF
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D019040:E-Selectin; D015870:Gene Expression; D006801:Humans; D006968:Hypersensitivity, Delayed; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009020:Morphine