AIM: To investigate the ability of Chinese cobra snake venom-metalloproteinase(MT) to induce the histamine release from human mast cells and its potential mechanisms.METHODS: MT was purified from the snake venom by using heparin agarose and Superdex75 chromatography.Mast cells were dispersed from human lung, colon and tonsil tissues after digestion with collagenase and hyaluronidase.The dispersed mast cells were then challenged with MT,stimulus and control in LP4 tubes for 15 min at 37 ℃.A glass fibre-based fluorometric assay was used to measure histamine in the supernatants of dispersed mast cells.RESULTS: MT induced a dose-dependent release of histamine from human colon,lung and tonsil mast cells.As low as 0.03(mg/L) of MT was able to stimulate significant histamine release from human colon mast cells,but a minimum of 0.3 or 30 mg/L of MT was required to stimulate a similar level of histamine release from lung or tonsil mast cells,respectively.The release of histamine from colon and lung mast cells in response to MT was maximized at 12 min following the addition of the stimulus.This was quite different from the picture of the peak histamine release from tonsil mast cells,in which histamine release was maximized at 8 min following the addition of MT.Pretreatment of cells with metabolic inhibitors and pertussis toxin reduced dramatically histamine release from human colon,lung and tonsil mast cells by MT.In exogenous Ca~(2+) and Mg~(2+) free experiments,the release of histamine induced by MT was significantly decreased.CONCLUSION: Cobra snake venom MT induces human mast cells to release histamine through a G-protein-related mechanism,which may contribute to the pathogenesis of venomous snake bite.