Objective To identify the resistance mechanism of mice to minimal lethal dose (MLD) of E.coli by transfection of BPI_ 700
-Fcγ1_ 700 chimeric gene. Methods Endotoxin neutralization, opsonization test, bacteria counting and pathological microscopy of vascular damage in test animals were carried out by routine technology as referenced. Result (1) The chimeric target protein in serum of the target gene
transferred mice killed E.coli and neutralized endotoxin, and showed activity of opsonization. (2) The bacterium number in serum and main viscera, endotoxin level in serum of the transferred mice were markedly less than those of controls. (3) Twelve hours after MLD E.coli challenge, the endotoxin level and the production of proinflammatory cytokines(TNF-α, IL-1β)in the serum of the control mice were markedly higher than that of transferred mice. (4) Pathological profile was proved as found in dead mice. Conclusion The mice transferred by AAV2-BPI_ 700 -Fcγ1_ 700 chimeric gene can resist MLD E.coli
infection and endotoxin induced by this infection through expressing chimeric target protein BPI_ 1-199 -Fcγ1. Our findings support the clinical application of antimicrobial gene therapy on bacterial infection, and offer an experimental basis for the application of gene therapy to individuals at high risk of infection.