Blocking the Terminal Complement pathway to preserve kidney function following renal IRI?

Summary of Bongoni, A et al; Complement-mediated Damage to the Glycocalyx Plays a Role in Renal Ischemia-reperfusion Injury in Mice. Transplantation Direct 2019.

 

The impact of complement activation was investigated on glycocalyx integrity and renal dysfunction in a mouse model of renal IRI (Ischemia-Reperfusion Injury). Animals were tested on renal function, complement activation, glycocalyx damage, endothelial cell activation, inflammation, and infiltration of neutrophils and macrophages. Results showed that treatment with antibody Mouse C5 (clone BB5.1), just before ischemia, decreased for example plasma levels of for example C3b and C5a. Immunofluorescence experiments to determine the deposition of C3b/c and tubular C9 showed reduced deposition after treatment with BB5.1 as well.

To characterize local renal inflammation inflitration of Ly-6G-positive neutrophils and F4/80-positive macrophages was measured with immunofluorescence. Sham-operated kidneys showed no or very few cells, while renal IRI induced significant recruitment of neutrophils. This infiltration was reduced in mice treated with BB5.1.

Together with even more results Bongoni et al found that IRI-induced renal dysfunction is strongly associated with complement activation, complement-mediated endothelial glycocalyx damage, and innate immune cell infiltration. Data with inhibition of C5 showed that the terminal pathway of complement has an important role in the injury process. Therefore, effective complement inhibition, by blocking the terminal pathway of complement, may prevent destruction of the glycocalyx and inflammation, thereby preserving kidney function following renal IRI.

More information about the used products?

- C5, Mouse, clone BB5.1

- C3b, Mouse, ELISA kit

- Neutrophils, Mouse, clone NIMP-R14

- Macrophages F4/80, Mouse, mAb BM8