# Mechanisms of Complement Dependent Immune Complex-Mediated Glomerulonephritis

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $235,341

## Abstract

PROJECT SUMMARY
The kidney is an immunologically active organ the size of a human fist (0.5% body weight). Yet 20‐25 % of
cardiac output traverses the kidney rendering it vulnerable to injury and loss of renal function. In renal diseases,
complement (C) activation and macrophage (MØ) infiltration are two crucial events that occur. Both facets can
be beneficial or detrimental, and behave differently at different locations depending on the microenvironment.
Complement signaling directs MØ to sites of inflammation and participates in local MØ amplification, the
numbers of which correlate negatively with renal function. Although MØ and C are intertwined, we are only
beginning to understand how these two facets of inflammation interact. Gaining insight into the mechanisms at
play in the regulation of trafficking and polarization of MØ by complement will open avenues for identification of
novel therapeutics for kidney diseases that have no effective therapies. With the advent of advanced technology
and better disease models, we are beginning to make inroads into better understanding glomerular, MØ and
complement biology and the changes that occur during disease. The goal of the work proposed here is to
understand glomerular inflammation using FH dependent immune complex mediated glomerulonephritis
(ICGN) model. Our preliminary studies show that there is significant increase in recruitment of MØ and T
lymphocytes across the glomerular filtration barrier, resulting in chronic inflammation that leads to fibrosis and
functional renal failure in FH dependent ICGN. Based on our results, our hypothesis is that signaling through
complement receptors leads to recruitment of MØ precursors to the kidney and alteration of MØ in the kidney,
where they aggravate disease pathology. To test this hypothesis, we will (a) determine the role of MØ in FH
dependent ICGN, (b) determine the impact of complement associated signaling on MØ in FH-dependent ICGN,
and (c) determine the role of complement, Mo/MØ and glomerular/endothelial barrier (GEB) in FH-dependent
ICGN. Our model of FH-dependent ICGN and GEB in culture are unique, with experimental features that are
unrivaled. Thus, our studies using these models can provide considerable insights into mechanisms of disease
relevant to human beings. We are well positioned to perform the proposed work, having all the necessary and
innovative models (in vivo and in vitro) and validated technologies to interrogate these cells and pathways (e.g.
molecular imaging, bone marrow transplants, genetic models and 18-color FACS analysis). We have also
assembled a team of experts in macrophage biology, vascular biology, imaging and leukocyte trafficking, to
accomplish our goals.

## Key facts

- **NIH application ID:** 9952368
- **Project number:** 5R01DK111222-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Jessy J Alexander
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,341
- **Award type:** 5
- **Project period:** 2018-08-17 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952368

## Citation

> US National Institutes of Health, RePORTER application 9952368, Mechanisms of Complement Dependent Immune Complex-Mediated Glomerulonephritis (5R01DK111222-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952368. Licensed CC0.

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