title: Changes in polysialic acid expression on myeloid cells during differentiation and recruitment to sites of inflammation: role in phagocytosis.
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.
authors.affiliation: Institute of Human Virology Department of Medicine and nstamatos@ihv.umaryland.edu.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Stamatos
authors.affiliation: Department of Medicine and.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Biochemistry and Genetics, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Jokilammi
authors.affiliation: 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.
authors.forename: Jukka
authors.initials: J
authors.lastname: Finne
authors.affiliation: Department of Medicine and.
authors.forename: Wilbur H
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Abderrahman
authors.initials: A
authors.lastname: El-Maarouf
authors.affiliation: Department of Medicine and.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Cross
authors.affiliation: Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD 21201, USA.
authors.forename: Kim G
authors.initials: KG
authors.lastname: Hankey
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D006410:Hematopoiesis; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: D019002:CD56 Antigen; D039943:Neuropilin-2; D012333:RNA, Messenger; D012794:Sialic Acids; C021319:polysialic acid
keywords: NCAM−/− and NRP-2−/− mice; macrophages; neuropilin-2; phagocytosis; polysialic acid