Complement alternative pathway activation in the autologous phase of nephrotoxic serum nephritis.

Abstract

The complement cascade is an important part of the innate immune system, but pathological activation of this system causes tissue injury in several autoimmune and inflammatory diseases, including immune complex glomerulonephritis. We examined whether mice with targeted deletion of the gene for factor B (fB(-/-) mice) and selective deficiency in the alternative pathway of complement are protected from injury in the nephrotoxic serum (NTS) nephritis model of antibody-mediated glomerulonephritis. When the acute affects of the anti-glomerular basement membrane antibody were assessed, fB(-/-) mice developed a degree of injury similar to wild-type controls. If the mice were presensitized with sheep IgG or if the mice were followed for 5 mo postinjection, however, the fB(-/-) mice developed milder injury than wild-type mice. The immune response of fB(-/-) mice exposed to sheep IgG was similar to that of wild-type mice, but the fB(-/-) mice had less glomerular C3 deposition and lower levels of albuminuria. These results demonstrate that fB(-/-) mice are not significantly protected from acute heterologous injury in NTS nephritis but are protected from autologous injury in response to a planted glomerular antigen. Thus, although the glomerulus is resistant to antibody-initiated, alternative pathway-mediated injury, inhibition of this complement pathway may be beneficial in chronic immune complex-mediated diseases.

• Authors: Joshua M Thurman, Svetlana N Tchepeleva, Mark Haas, Sarah Panzer, Susan A Boackle, Magdalena J Glogowska, Richard J Quigg, V Michael Holers
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 302 Issue 12 Pg. F1529-36 (Jun 15 2012) ISSN: 1522-1466 [Electronic] United States
• PMID: 22492944 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Complement C3
• Complement Factor B

Topics

• Animals
• Complement C3 (immunology)
• Complement Factor B (genetics)
• Complement Pathway, Alternative (physiology)
• Disease Models, Animal
• Kidney Glomerulus (immunology, pathology)
• Mice
• Mice, Knockout
• Nephritis (immunology, pathology)
• Proteinuria (immunology, pathology)