EXPERIMENTAL IMMUNOGLOBULIN-A NEPHROPATHY INDUCED BY GRAM-NEGATIVE BACTERIA

A study was conducted to determine whether intraperitoneal and oral ad ministration of formalin-fixed gram-negative bacteria induced immunohi stologically and ultrastructurally evident glomerular deposition of Ig A and C3 in C3H/HeN mice. Separate treatments with strains of Pseudomo nas aeruginosa, Escherichia coli, Haemophilus influenzae, Klebsiella p neumoniae, and two kinds of lipopolysaccharide (LPS) were used. Two mi ce in each treatment group were sacrificed at 10, 20 and 30 weeks of a ge to examine sequential glomerular changes. In addition to the intrap eritoneal administration (IP) groups receiving whole formalin-fixed ba cterial cells, cell precipitate and supernatant fractions of each bact erial strain after sonication were injected intraperitoneally once a w eek, and the mice were sacrificed at 30 weeks of age. Sequential quant itation or IgG, IgA or IgM in serum and the isotypes specific for each of the bacterial strains or LPS administered was performed by ELISA. The incidence of immunofluorescence positivity for glomerular IgA and C3 was 37-71 and 37-66.7%, respectively, in the IP groups that had rec eived bacterial cells of each strain, which was significantly higher t han that in the IP groups given LPS or in the controls. These results suggest that cell wall components common among gram-negative bacteria, other than LPS, play a major role in the glomerular deposition of IgA and C3. This is the first use of gram-negative bacteria to establish an active model of IgA nephropathy.