# Influence of polysialic acid on leukocyte migration

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $499,945

## Abstract

PROJECT SUMMARY
Changes in the glycosylation pattern of cell surface proteins and lipids are increasingly being recognized as an
important factor in controlling cellular activity. There is growing interest in how these changes can be regulated
to affect physiologic processes in health and disease. The goal of this proposal is to understand how a specific
carbohydrate modification on the surface of cells of the immune system influences the function of these cells
during states of inflammation and infection. As a key member of cellular innate and adaptive immune
responses, monocytes are recruited to pulmonary sites of infection where they differentiate into macrophages
and dendritic cells before migrating through the lymphatic system. This targeted migration and programmed
maturation of monocytes and monocyte-derived cells is guided by specific, highly-organized cell-cell and
receptor-ligand interactions, many of which are modulated by glycosylation of cell surface receptors and
adhesion molecules. Polysialic acid (polySia) is a unique glycan modification of at least three such proteins,
neural cell adhesion molecule (NCAM/CD56), neuropilin-2 (NRP-2), and E-selectin ligand-1 (ESL-1), that are
expressed at different stages of monocyte maturation. We will test the hypothesis that regulated expression of
polySia on monocytes as they differentiate into macrophages and dendritic cells, and on neutrophils that also
are polysialylated, helps direct cell homing and a well-orchestrated immune response during pulmonary
infection with viral and bacterial pathogens. Mice that are deficient in expression of the enzyme that
synthesizes polySia in leukocytes (ST8 SiaIV-/-) and of the carrier proteins (NCAM/CD56-/- and NRP-2-/-) will
be used for in vitro and in vivo studies. Our Specific Aims will i) establish the impact in vivo of polySia on
monocytes, macrophages, DC and neutrophils in the targeted immune response in a murine model of bacterial
and viral pneumonia; ii) define the mechanism(s) through which polysialylated proteins on the surface of
human and murine monocytes, macrophages, DC and neutrophils control adhesion to and migration across
pulmonary microvascular monolayers; and iii) define and analyze the regulated expression of polySia and of
polysialylated proteins during differentiation of primary monocytes into DC and macrophages. We expect to
identify specific cell-cell and receptor-ligand interactions that polySia promotes or interferes with during
different stages of the monocyte/macrophage/dendritic cell maturation and migratory processes, as well during
neutrophil recruitment. The results from our studies will provide a blueprint to engineer levels of expression of
polySia and/or carrier proteins in myeloid cells in order to optimize migration to and from sites of
infection/inflammation to improve the overall immune response.

## Key facts

- **NIH application ID:** 10450169
- **Project number:** 5R01AI132733-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** NICHOLAS MILTON STAMATOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $499,945
- **Award type:** 5
- **Project period:** 2018-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450169

## Citation

> US National Institutes of Health, RePORTER application 10450169, Influence of polysialic acid on leukocyte migration (5R01AI132733-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10450169. Licensed CC0.

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