This study is to investigate certain biological activities of meningococcal endotoxin in different physical forms such as purified LOS, LOS in outer membrane vesicles and associated with outer membrane proteins from the wild strain M986 (encapsulated), its mutants M986-NCB and OP-(an LOS mutant), both non-encapsulated.To evaluate the toxic levels of the LOS in these physical forms, groups of B6D2F1 mice were sensitized with D-Galactosamine and then administered one of the endotoxin preparations within 30 mins. The LD50 was determined, and the results indicated that purified LOS from the three strains (M986, M986(NCV)), and OP- were about 3 times more toxic than the LOS in their outer membrane vesicles and more than 300 times more toxic than the LOS bound with outer membrane proteins.To explore the possible mode of action of the LOS in these preparations, we examined the functions of mouse peritoneal macrophages following exposure to LOS in vivo. Elicited peritoneal macrophages from animals pretreated with these LOS preparations in route at various doses (50ng-75ug/mouse) effectively killed miningococci strain M986 in vitro. Repeated treatment dramatically enhanced the microbial killing capacity of the macrophages. Macrophages from the LOS tolerized mice produced significantly less TNF in response to purified LOS ex vivo than cells from control animals. IL- 6 was induced in all pretreated goups but was most pronounced in purified LOS pretreated groups. Furthermore, the effects of LOS on the peripheral blood and myeloid cells were examined, and we found that the OP-LOS was the most potent in terms of cell proliferation and differentiation.
