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In previous research, chimerical BPI23-Fcγ1 gene which consisted of human bactericidal/permeability increasing protein (BPI) gene of encoding the functional N terminus (amino acid residues 1 to 199) of human BPI and Fcγ1 gene of encoding the Fc segment of human immunogiobulin G1 was successfully reconstructed within a recombinant adeno-associated virus serotype 2 (rAAV2) vector as rAAV2-BP123-Fcγ1. Here, to evaluate the potentiality of applying gene therapy to gram negative bacterial (GNB) infection in high-risk patients, we investigated protection of immuno-compromised mice and immunocompetent mice from challenge with minimal lethal dose (MLD) KiebsieUa pneumonia infection after rAAV2-BPI23-Fcγ1 gene transferred. The results showed that the survival rate of rAAV2-BPI23-Fcγ1 transferred immunocompetent mice as well as immuno-compromised mice (40.0% and 44.4%, respectively) were significant higher than that of corresponding control mice (6.7% and 4.4%, respectively); the bacteria counting, level of endotoxin and proinflammatory cytokines in the rAAV2-BPI23-Fcγ1 transferred immuno-compromised mice were markedly lower than that of rAAV2-EGFP and rAAV2-Null transferred immuno- compromised mice. Our data suggest that rAAV2-BPI23-Feγ1 gene transferring offered immuno-compromised mice with resistance against GNB infection, so it is quite potential in preventing GNB infection of clinical high-risk patients. Cellular & Molecular lmmunology. 2008;5(6):439-445.