Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin.
Tumour necrosis factor-alpha (TNF-alpha)/cachectin is a multifunctional cytokine that has effects in inflammation, sepsis, lipid and protein metabolism, haematopoiesis, angiogenesis and host resistance to parasites and malignancy. TNF-alpha was first described in activated macrophages, but certain mouse or rat mast cell populations (reviewed in refs 4,5) and some in vitro-derived human cells with cytochemical features of mast cells-basophils may also contain products similar to TNF-alpha. Here we present evidence that resident mouse peritoneal mast cells constitutively contain large amounts of TNF-alpha bioactivity, whereas cultured, immature mast cells vary in their TNF-alpha content. IgE-dependent activation of cultured or peritoneal mast cells induces extracellular release of TNF-alpha and augments levels of TNF-alpha messenger RNA and bioactivity. These findings identify mouse mast cells as an important source of both preformed and immunologically inducible TNF-alpha, and suggest that release of TNF-alpha by mast cells may contribute to host defence, the pathophysiology of allergic diseases and other processes dependent on TNF-alpha.
Gordon
J R
JR
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215.
Galli
S J
SJ
D000818:Animals; D000941:Antigens / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000941:Antigens; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D007073:Immunoglobulin E; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate