# Decay accelerating factor (CD55) protects against lectin pathway-mediated AT2 cell dysfunction in cigarette smoke-induced emphysema

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 2023 · $760,358

## Abstract

Project summary
The mechanisms by which cigarette smoke (CS) activates the complement cascade to cause distal lung sterile
injury and progression to COPD are not completely understood. Considering the critical role of complement in
pathogen-induced inflammation, selective inhibition of the lectin complement pathway may result in decreased
CS-induced emphysema-like airspace enlargement without an indiscriminate inhibition of complement’s
response to pathogens. In Aim 1 we propose to investigate a novel mechanism of CS-induced lung injury,
focusing on members of the lectin complement pathway that are necessary to induce complement deposition
in the lung, decreased type-2 alveolar epithelial (AT2) cell proliferation and differentiation into AT1 cells,
resulting in emphysema. In Aim 2 we will investigate whether decay accelerating factor (CD55), a complement
regulator is necessary and required to protect against lectin complement deposition on AT2, preventing cell
injury and improving AT2 proliferation / differentiation. In Aim 3 we propose a translational approach to develop
a plasma complement activity score encompassing complement proteins and their regulators that could identify
emphysema progression in smokers at risk and early COPD individuals. My proposal addresses the clinically
relevant question whether harnessing membrane CD55 expression and signaling in AT2 cells can prevent
lectin complement deposition and improve AT2 proliferation and differentiation mitigating emphysema
development. Our ex-vivo and in-vivo murine studies are accompanied by measurements of complement
proteins and regulators levels and activity in plasma from active smokers with and without COPD enrolled in
COPDGene using a multiplex proteomic platform, SomaScan. Multiple complement SomaScan proteins are
used to develop a “complement activity score” to help predict emphysema progression.
Completion of this project will provide compelling experimental evidences that targeting lectin pathway
activation and preserving membrane CD55 expression on AT2 cells ameliorates distal lung injury in murine
models of emphysema and it can be harnessed as next generation biomarkers in human COPD disease. Our
newly complement activity score could identify smokers at risk and early COPD subjects in future research and
pharmacological clinical trials. The complementary expertise of our team, the translational aspect of the
proposal, and access to well-phenotyped human specimens increase the relevance and chance of successful
completion of this project.

## Key facts

- **NIH application ID:** 10737359
- **Project number:** 1R01HL166828-01A1
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Karina Serban
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $760,358
- **Award type:** 1
- **Project period:** 2023-07-01 → 2023-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10737359

## Citation

> US National Institutes of Health, RePORTER application 10737359, Decay accelerating factor (CD55) protects against lectin pathway-mediated AT2 cell dysfunction in cigarette smoke-induced emphysema (1R01HL166828-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10737359. Licensed CC0.

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