# Role of CXCR2-mediated cell trafficking in pulmonary vascular remodeling

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $381,250

## Abstract

PROJECT SUMMARY
It is unknown how myeloid or endothelial cell expression of CXCR2 contributes to myeloid-derived suppressor
cell (MDSC) recruitment to the lungs, with subsequent pulmonary vascular remodeling. There is an urgent need
to close this gap in knowledge because, until accomplished, immunotherapeutic modulation of CXCR2 contribu-
tion to the development of vascular remodeling, and pulmonary hypertension (PH), will likely remain beyond
reach. The overall objective here is to define the contribution of MDSC recruitment through chemokine receptor
CXCR2, expressed by either circulating myeloid cells or the pulmonary vascular endothelium. The central hy-
pothesis is that tissue specific CXCR2 expression is necessary for polymorphonuclear (PMN)-MDSC recruitment
to the pulmonary vasculature and PH development. The scientific premise for this hypothesis has been formu-
lated on the basis of preliminary data demonstrating that MDSCs expressing CXCR2 are necessary for devel-
opment of PH in animal models of pulmonary vascular disease, and that this circulating cell population is present
to a higher degree in whole blood of idiopathic pulmonary fibrosis (IPF) patients with PH, compared to IPF pa-
tients without elevated pulmonary pressures. The rationale for the proposed research is that, upon completion
of experiments, future studies can be proposed taking advantage of University of Florida expertise in tissue-
specific delivery of either existing CXCR2 inhibitors though use of nanoparticle technology, or CXCR2 directed
gene-therapy utilizing AAV vectors. Expected outcomes, as a consequence of proposed work, are a vertical
advancement in the understanding of CXCR2 contribution to vascular remodeling, additionally establishing a
foundation for future studies detailing mechanisms of MDSC mediated PH development related to chronic lung
disease, such as IPF. The results are expected to have positive translational impact because it is probable that
the identified tissue-specific CXCR2 influence will provide targets for immunotherapeutic interventions. The cen-
tral hypothesis will be tested by pursuing the following specific aims: 1) test the hypothesis that CXCR2 expres-
sion by PMN-MDSC promotes development of PH, and 2) test the hypothesis that vascular endothelial cell
CXCR2 expression is protective against MDSC recruitment in PH. In the first aim, wild type and transgenic mice
with tissue-specific deletion of CXCR2 in myeloid-derived cells (LysM.Cre-CXCR2fl/fl, mCXCR2 mice) will be
used to determine the effect that attenuated MDSC trafficking will have on the development of PH in two models
of disease (bleomycin-induced pulmonary fibrosis and chronic hypoxia). In the second aim, transgenic mice with
tissue-specific deletion of CXCR2 in vascular endothelial cells (VECad.Cre-CXCR2fl/fl, eCXCR2 mice) will be
used in the bleomycin and hypoxia models of PH. The contribution of these studies will be significant because it
represents a strategy to improv...

## Key facts

- **NIH application ID:** 10692849
- **Project number:** 5R01HL142776-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Andrew Justin Bryant
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2019-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10692849

## Citation

> US National Institutes of Health, RePORTER application 10692849, Role of CXCR2-mediated cell trafficking in pulmonary vascular remodeling (5R01HL142776-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10692849. Licensed CC0.

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