title: The innate pattern recognition molecule Ficolin-1 is secreted by monocytes/macrophages and is circulating in human plasma.
abstract: Ficolin-1 (M-Ficolin) is a pattern recognition molecule of the complement system that is expressed by myeloid cells and type II alveolar epithelial cells. Ficolin-1 has been shown to localize in the secretory granules of these cells and attached to cell surfaces, but whether Ficolin-1 exists a soluble molecule in the extracellular environment or in plasma is unknown. In this study we explored the possibility that Ficolin-1 may be secreted from monocytes, macrophages or immature dendritic cells and may exist in human plasma. Expression of Ficolin-1 was analyzed using real-time quantitative PCR and SDS-PAGE/western blot. Secretion of Ficolin-1 was investigated in cells and plasma from healthy donors through affinity purification using N-acetyl-d-glucosamine-agarose beads and ELISA. Ficolin-1 was found differentially expressed and synthesised by monocytes, macrophages and immature dendritic cells. Notably monocytes and macrophages, but not immature dendritic cells are able to secrete Ficolin-1 into the extracellular environment. Moreover, Ficolin-1 was detected in human plasma from healthy donors with a median concentration of 60.5 ng/ml ranging from 45.7 to 100.4 ng/ml. We show that Ficolin-1 is secreted into the extracellular environment from human monocytes/macrophages, but not immature dendritic cells. Importantly, these results demonstrate that Ficolin-1 exists in human plasma and serum under normal conditions, hereby revising the general assumption that Ficolin-1 is solely a cellular associated protein.
authors.affiliation: Department of Clinical Immunology, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Honoré
authors.forename: Sara
authors.initials: S
authors.lastname: Rørvig
authors.forename: Lea
authors.initials: L
authors.lastname: Munthe-Fog
authors.forename: Tina
authors.initials: T
authors.lastname: Hummelshøj
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D016466:CHO Cells; D011232:Chemical Precipitation; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D037102:Lectins / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D000097604:Ficolins
chemical_list: D000911:Antibodies, Monoclonal; D037102:Lectins; D012333:RNA, Messenger; D000097604:Ficolins