Histamine-releasing factor generated by the interaction of endotoxin with hamster serum

Injection of hamsters with endotoxin (LPS) resulted, 4 to 14 days later, in a marked decline in the mast cell count and in a reduction of the available histamine content of cells obtained by peritoneal lavage. The release of histamine from isolated peritoneal hamster mast cells in vitro could be achieved by incubating LPS with fresh hamster serum followed by addition of mast cells and a second incubation. The generation of a histamine-releasing factor from serum could be inhibited by conditions which inhibit the consumption of complement by LPS. Several substances could be substituted for LPS in the generation of histamine-releasing activity including heat-aggregated human gamma globulin, zymosan, purified cobra venom factor, and washed antigen-antibody precipitates. With all of these agents, the generation of a histamine-releasing substance from hamster serum was accompanied by consumption of hemolytic complement. The results suggest that LPS indirectly leads to the release of histamine from mast cells as a result of interactions with the complement system.