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Glycobiology. 2014 Sep;24(9):864-79. doi: 10.1093/glycob/cwu050. Epub 2014 May 27.

Changes in polysialic acid expression on myeloid cells during differentiation and recruitment to sites of inflammation: role in phagocytosis.

Author information

1
Institute of Human Virology Department of Medicine and nstamatos@ihv.umaryland.edu.
2
Department of Medicine and.
3
Department of Medical Biochemistry and Genetics, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland.
4
Department of Medical Biochemistry and Genetics, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland Department of Biosciences, University of Helsinki, PO Box 56, FI-00014 Helsinki, Finland.
5
Department of Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
6
Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD 21201, USA.

Abstract

Polysialic acid (polySia) is a unique linear homopolymer of α2,8-linked sialic acid that has been studied extensively as a posttranslational modification of neural cell adhesion molecule in the central nervous system. Only two proteins are known to be polysialylated in cells of the immune system: CD56 on human natural killer cells and murine bone marrow (BM) leukocytes, and neuropilin-2 (NRP-2) on dendritic cells (DCs). We tested the hypothesis that polySia expression is regulated during maturation and migration of leukocytes and plays a role in functional activity. Using wild-type and NCAM(-/-) mice, we show that BM neutrophils express only polysialylated CD56, whereas a subset of BM monocytes expresses polysialylated CD56 and/or another polysialylated protein(s). We demonstrate that polysialylated CD56 expression is progressively down-regulated in wild-type monocytes and monocyte-derived cells during migration from BM through peripheral blood to pulmonary and peritoneal sites of inflammation. Freshly isolated monocyte-derived peritoneal macrophages are devoid of polySia yet re-express polySia on NRP-2 and an additional protein(s) after maintenance in culture. Removal of polySia from these cells enhances phagocytosis of Klebsiella pneumoniae, suggesting that down-regulation of polySia on macrophages facilitates bacterial clearance. Using wild-type and NRP-2(-/-) mice, we demonstrate that NRP-2 and an additional protein(s) are polysialylated by ST8 SiaIV in BM-derived DCs. We conclude that polySia expression in monocyte-derived cells is dynamically regulated by ST8 SiaIV activity and by expression of carrier proteins during recruitment to sites of inflammation and influences cellular interactions with microbes, contributing to innate and adaptive immune responses.

KEYWORDS:

NCAM−/− and NRP-2−/− mice; macrophages; neuropilin-2; phagocytosis; polysialic acid

PMID:
24865221
PMCID:
PMC4116047
DOI:
10.1093/glycob/cwu050
[Indexed for MEDLINE]
Free PMC Article

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