# Mannose binding lectin-dependent complement activation in emphysema

> **NIH NIH K08** · NATIONAL JEWISH HEALTH · 2020 · $158,652

## Abstract

Project summary
The mechanisms by which cigarette smoke (CS) activates the complement cascade to cause lung sterile
inflammation and COPD progression are not completely understood. Considering the critical role of
complement in pathogen-induced inflammation, selective inhibition of the mannose-binding lectin (MBL)
complement pathway may result in decreased CS-induced inflammation and 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 whether mannose-binding lectin
associated serine protease-2 (MASP-2), the central protease in the MBL pathway, is necessary to induce
inflammation and emphysema during CS exposure. In Aim 2 we will investigate whether alpha-1 antitrypsin, a
major serine protease inhibitor, binds and inhibits MASP-2. My proposal addresses the clinically relevant
question whether selective targeting of complement cascade via MASP-2 inhibition ameliorates lung
inflammation and emphysema development in relevant murine models of CS exposure. Our animal studies are
complemented by measurements of MASP-2 levels and activity in samples from active smokers with and
without COPD.
The design and implementation of the proposed coursework and experiments will assist me in gaining
expertise in complement biology, enzymology, and perfect my skills in lung stereology. I will train in new
techniques, such as miscroscale thermophoresis, isothermal titration calorimetry, and fluorescence resonance
energy transfer, FRET - fluorescence lifetime imaging microscopy, FLIM to study alpha-1 antitrypsin binding to
MASP-2. These skills and the new research focus on the role of complement system in CS-induced sterile
inflammation will allow me to become an independent investigator in a different area of research than my
mentor, Dr. Petrache. My committee members and collaborators are strategically positioned to assist
me in completing this proposal. National Jewish Health environment, the extraordinary expertise of the
mentoring team, and the track record of fruitful collaborations between Dr. Petrache and members of the
committee, will ensure a multifaceted and nurturing setting to facilitate my transition to independence.
Completion of this project will provide compelling experimental evidences that MASP-2 inhibition using
protease inhibitors ameliorates inflammation and lung injury in murine models of emphysema and it can be
harnessed as next generation therapeutics in human COPD disease.

## Key facts

- **NIH application ID:** 9839664
- **Project number:** 5K08HL141770-02
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Karina Serban
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,652
- **Award type:** 5
- **Project period:** 2018-12-17 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9839664

## Citation

> US National Institutes of Health, RePORTER application 9839664, Mannose binding lectin-dependent complement activation in emphysema (5K08HL141770-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9839664. Licensed CC0.

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