Detection of venom factors releasing histamine from rat peritoneal mast cells

Venoms are known to contain many types of toxins. Some show direct cytotoxicity but not always to the same extent on each type of target cell tested. These experiments asked if venoms might be a source of factors which release histamine from mast cells. These factors would be proinflammatory and could thus significantly contribute to the pathology of snake bite envenomation. These might be either direct lytic factors described by their action on other cells but now found to be active on mast cells, or be previously undescribed, since the direct effects of venoms on mast cells have not been extensively explored. After establishing that a wide variety of venoms were effective at releasing histamine in this system, the toxin fractions (peptides below 10KD prepared using molecular filtration membranes) were examined both for proportion of total venom (based on A²¹⁴ and A²⁸⁰ ) and for histamine releasing activity. Of the forty venoms tested, the cobra venoms were most active, showing kinetics of activity consistent with peptide toxins. One cobra venom selected for size exclusion analysis contained a unique low molecular weight peak of activity in addition to what is presumably the known cytotoxins. Other venoms in several phylogenetic groups also showed significant activity. These studies: indicate that cobra venom peptides of the size of the cobra cytotoxins are active upon mast cells; that also active are other venom toxins which may be factors known for activity on other cells or known by another activity altogether than cytotoxicity; and are consistent with the interpretation that there may also be other significant undescribed histamine releasing factors present among venoms.