Tethering of Ficolin-1 to cell surfaces through recognition of sialic acid by the fibrinogen-like domain

Journal of Leukocyte Biology

Christian Honoré¹  Mikkel-Ole Skjoedt¹  Tina Hummelshøj¹  Niels Borregaard²  Sara Rørvig²  Peter Garred¹ 

[1] Laboratory of Molecular Medicine, Department of Clinical Immunology, Sect. 7631, and Laboratory of Molecular Medicine, Department of Clinical Immunology, Sect. 7631, and Laboratory of Molecular Medicine, Department of Clinical Immunology, Sect. 7631, and;Granulocyte Research Laboratory, Department of Haematology, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark Granulocyte Research Laboratory, Department of Haematology, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark Granulocyte Research Laboratory, Department of Haematology, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

关键词: complement;    innate immunity;    lectin pathway;    MBL/ficolin-associated serine protease;    mannose-binding lectin;    FCN1;    FCN2;    ligand;   

DOI  :  10.1189/jlb.1209802

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown