CYTOTOXICITY OF ANTHRAX LETHAL FACTOR MICROINJECTED INTO MACROPHAGE CELLS THROUGH SENDAI-VIRUS ENVELOPES

Lethal toxin (LT) secreted by Bacillus anthracis consists of two prote ins, protective antigen (PA) and lethal factor (LF). LT causes lysis o f macrophages and derived cell lines at low concentrations. PA binds t o the cell surface receptors and mediates translocation of LF into cyt osol of mammalian cells. Internalization of LF into cytosol by osmotic lysis of pinocytic vesicles requires high concentration of LF for cel l lysis. To examine the possible cell lysis by LF at low concentration , we introduced LF directly into cytosol of J774A.1 cells through reco nstituted Sendai virus envelopes. The introduction of LF lysed J774A.1 cells in a concentration dependent manner. Internalization of PA alon e through virosome had no toxic effect on J774A. 1 cells. In the proce ss of cytotoxicity LF was not cleaved by cellular proteases. Unlike ma ny protein toxins, golgi was not involved in the expression of lethal toxin activity. These results indicate that LF is the toxic component of anthrax lethal toxin and prior proteolytic processing or traffickin g through golgi is not required for its activity.