title: Antibody-mediated glomerulonephritis in mice: the role of endotoxin, complement and genetic background.
abstract: Antibody-mediated glomerulonephritis in man may be exacerbated by infection and this effect may be mediated by bacterial endotoxin. There is evidence supporting a role for endotoxin in heterologous nephrotoxic nephritis in rats, but the role of endotoxin in this model in mice has not previously been explored. Previous data in mice on the role of complement in this model are conflicting and this may be due to the mixed genetic background of mice used in these studies. We used the model of heterologous nephrotoxic nephritis in mice and explored the role of endotoxin, complement and genetic background. In this study we show a synergy between antibody and endotoxin in causing a neutrophil influx. We also show that C1q-deficient mice have an increased susceptibility to glomerular inflammation but this is seen only on a mixed 129/Sv x C57BL/6 genetic background. On a C57BL/6 background we did not find any differences in disease susceptibility when wildtype, C1q, factor B or factor B/C2 deficient mice were compared. We also demonstrate that C57BL/6 mice are more susceptible to glomerular inflammation than 129/Sv mice. These results show that endotoxin is required in this model in mice, and that complement does not play a major role in glomerular inflammation in C57BL/6 mice. C1q may play a protective role in mixed-strain 129/Sv x C57BL/6 mice, but the data may also be explained by systematic bias in background genes, as there is a large difference in disease susceptibility between C57BL/6 and 129/Sv mice.
authors.affiliation: Division of Medicine and Department Histopathology, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK. michael.robson@kcl.ac.uk
authors.forename: M G
authors.initials: MG
authors.lastname: Robson
authors.forename: H T
authors.initials: HT
authors.lastname: Cook
authors.forename: C D
authors.initials: CD
authors.lastname: Pusey
authors.forename: M J
authors.initials: MJ
authors.lastname: Walport
authors.forename: K A
authors.initials: KA
authors.lastname: Davies
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015922:Complement C1q / Q000235:genetics / Q000276:immunology; D003175:Complement C2 / Q000235:genetics; D011415:Complement Factor B / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility; D004768:Enterotoxins / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*
chemical_list: D000906:Antibodies; D003175:Complement C2; D004768:Enterotoxins; D015922:Complement C1q; D011415:Complement Factor B