Description
Ficolins are a group of proteins containing both a collagen-like domain and a fibrinogen-like domain. Three forms of Ficolin have been identified in humans: Ficolin-1 (M-ficolin), Ficolin-2 (L-ficolin) and Ficolin-3 (H-ficolin 3). Ficolin-3, also known as Hakata-antigen or H-ficolin, is composed by a collagen-like strand and three C-terminal recognition domains which bind to acetyl groups on microbial surfaces such as GlcNAc or GalNAc. Ficolin-3 is synthesized both in the liver, from where it is secreted into the blood circulation, and in the lung. Similar to MBL and Ficolin-2, Ficolin-3 relies on MBL-associated serine protease 2 (MASP-2) for activation of the complement system. After binding of Ficolin-3/MASP-2 complexes to microbial surfaces, MASP-2 sequentially cleaves C4 and C2, thereby generating the C3 convertase C4bC2b, which finally leads to opsonization and direct lysis of pathogens and recruitment of inflammatory cells. Ficolin-3 is present in serum at mean concentration of 15 µg/ml, with only minor variations. Ficolin-3 was present in all sera from more than 150,000 individuals tested, except in some systemic lupus erythromatosis patients. Approximately 5% of systemic lupus erythromatosis patients were found to be Ficolin-3 negative, probably owing to the presence of anti-Ficolin-3 autoantibody. In 398 patients with other autoimmune diseases, Ficolin-3 was always present. In liver disease the serum levels decreased with increasing severity of cirrhosis. Ficolin-3 bound to a population of late apoptotic cells, while a strong and uniform binding to necrotic cells was observed. The binding properties differed from those of MBL and Ficolin-2. Ficolin-3 binding to late apoptotic cells resulted in a significant increase in adhesion/uptake by macrophages