title: Tethering of Ficolin-1 to cell surfaces through recognition of sialic acid by the fibrinogen-like domain.
abstract: Three Ficolins have been identified in humans: Ficolin-1 (M-Ficolin), Ficolin-2 (L-Ficolin), and Ficolin-3 (H-Ficolin). Ficolin-1 is the least-described of the Ficolins and is expressed by monocytes, granulocytes, and in the lungs. Ficolin-1 is found circulating at low concentrations in serum but is regarded primarily as a secretory molecule that exerts its function locally in inflamed tissues. Ficolin-1 has been reported on the surface of monocytes and granulocytes and was suggested originally to function as a phagocytic receptor. However, the molecule does not contain any obvious transmembrane domain, and no binding partners have been identified. To gain further insight in the physiological role of Ficolin-1, we sought to identify the molecular mechanism responsible for the membrane association of Ficolin-1 to monocytes and granulocytes. We demonstrate that expression of Ficolin-1 on the cell surface is restricted to monocytes and granulocytes. Ficolin-1 is tethered to the cell surface of these cells through its fibrinogen-like domain, and the ligand involved in the binding of Ficolin-1 is shown to be sialic acid. Moreover, rFicolin-1 bound activated but not resting T lymphocytes. Together, these results demonstrate a novel self-recognition mechanism of leukocytes mediated by the fibrinogen-like domain of Ficolin-1.
authors.affiliation: Department of Clinical Immunology, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Honoré
authors.forename: Sara
authors.initials: S
authors.lastname: Rørvig
authors.forename: Tina
authors.initials: T
authors.lastname: Hummelshøj
authors.forename: Mikkel-Ole
authors.initials: MO
authors.lastname: Skjoedt
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D002118:Calcium / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism*; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D020298:U937 Cells; D000097604:Ficolins
chemical_list: D002118:Calcium; D005340:Fibrinogen; D037102:Lectins; D019158:N-Acetylneuraminic Acid; D011994:Recombinant Proteins; D000097604:Ficolins