15 Defining the impact of factor H, factor H-related 1, and factor H-related 5 on C3b deposition on mouse mesangial cells

Amanda Heiderscheit; Angela Nelson; Carla Nester; Yuzhou Zhang; Richard Smith

doi:10.1016/j.imbio.2023.152473

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15 Defining the impact of factor H, factor H-related 1, and factor H-related 5 on C3b deposition on mouse mesangial cells

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15 Defining the impact of factor H, factor H-related 1, and factor H-related 5 on C3b deposition on mouse mesangial cells

Amanda Heiderscheit, Angela Nelson, Carla Nester, Yuzhou Zhang and Richard Smith

Immunobiology (1979), Vol.228(5), p.152473

09/2023

DOI: 10.1016/j.imbio.2023.152473

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Abstract

The alternative pathway of complement is an integral part of the innate immune system that is constitutively active providing protection against foreign invaders in the human body. Mediators of its regulation, like Factor H, regulate amplification and prevent excessive activation, while Factor H-related 1 and Factor H-related 5 are thought to enhance the complement response. Balance between Factor H and Factor H-related proteins is therefore critical in controlling the intricate dance between clearance of pathogens and tissue inflammation and damage. As compared to controls, we have found that ratios of Factor H-related proteins to Factor H are elevated in patients with C3 glomerulopathy, an ultra-rare complement-mediated kidney disease. We therefore sought to define the impact of Factor H, Factor H-related 1, and Factor H-related 5 on mouse mesangial cells (MES13) using an in-house generated C3b deposition assay and tag-free Factor H and related proteins. We hypothesized Factor H would decrease C3b deposition on cell surfaces while Factor H-related 1 and Factor H-related 5 would have the opposite effect. Our results show that on MES13 cell surfaces: 1) the addition of Factor-H reduces or completely prevents C3b deposition; and 2) the addition of Factor H-related 5 drastically increases C3b deposition. From these results we can conclude the balance between Factor H and Factor H-related 5 may perpetuate the progression of C3 glomerulopathy. Similar work is currently ongoing with Factor H-related 1. (This work was supported in part by NIH Grant R01 DK110023 (CMN, RJS) and T32AI007485 (KL)).

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Title: Subtitle: 15 Defining the impact of factor H, factor H-related 1, and factor H-related 5 on C3b deposition on mouse mesangial cells
Creators: Amanda Heiderscheit - University of Iowa
Angela Nelson - University of Iowa
Carla Nester - University of Iowa
Yuzhou Zhang - University of Iowa
Richard Smith
Resource Type: Abstract
Publication Details: Immunobiology (1979), Vol.228(5), p.152473
DOI: 10.1016/j.imbio.2023.152473
ISSN: 0171-2985
eISSN: 1878-3279
Language: English
Date published: 09/2023
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984458104502771

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