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Factor H related proteins modulate complement activation on kidney cells
Brandon Renner1, Jennifer Laskowski1, Felix Poppelaars1
1Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.
Kidney International
|September 5, 2022
Summary
Factor H-related proteins (FHRs) impact kidney complement regulation differently. While all four tested FHRs caused in vitro complement dysregulation on kidney cells, only FHR E affected glomerular complement in vivo.
Area of Science:
- Immunology
- Nephrology
- Complement System Biology
Background:
- Factor H regulates the alternative complement pathway; its dysfunction is linked to glomerular injury.
- Factor H-related proteins (FHRs) are structurally similar to Factor H and implicated in glomerular diseases.
- The precise mechanisms by which FHRs influence kidney protection or injury remain unclear.
Purpose of the Study:
- To investigate the role of FHRs in regulating complement activation and dysregulation within the kidney.
- To characterize the differential interactions of FHRs with kidney cells and complement components.
Main Methods:
- Expression and purification of recombinant murine FHRs (A, B, C, and E).
- Assessment of FHR binding to heparin, C3d, and various kidney cell types (in vitro).
- Evaluation of complement dysregulation on kidney cell surfaces in vitro.
- In vivo studies involving FHR E injection in mice, including a model of ischemic acute kidney injury.
Main Results:
- All four FHRs exhibited distinct binding interactions with Factor H ligands and kidney cells.
- In vitro, all FHRs induced complement dysregulation on kidney cell surfaces, with varying magnitudes.
- In vivo, only FHR E caused glomerular complement dysregulation; it did not worsen ischemic acute kidney injury.
Conclusions:
- FHRs possess unique properties influencing complement regulation in the kidney.
- The effects of FHRs on complement are cell-type specific and context-dependent.
- FHR E demonstrates specific in vivo effects on glomerular complement, highlighting differential roles within the FHR family.
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