Ficolins are innate immune pattern‐recognition molecules. The name of ficolin was derived from its basic structure, consisting of a collagen‐like domain and a fibrinogen‐like domain (FBG). The FBG preferably recognises acetylated compounds. Humans have three homologous proteins: H‐ficolin (or ficolin‐3), L‐ficolin (or ficolin‐2) and M‐ficolin (or ficolin‐1). Mice have ficolin‐A and ficolin‐B, which are homologous to L‐ficolin and M‐ficolin, respectively, whereas a murine homologue of H‐ficolin is absent. Ficolin genes are germinally present and, therefore, their proteins are expressed at healthy state and are circulating in blood or localised in organs, affording an instant host protection. Ficolins are homologous to collectins structurally and functionally but has a difference in target recognition. Ficolins, like collectins, play important roles in innate immunity as activators of the lectin pathway of the complement system.

Key Concepts:

  • Ficolins are molecules of innate immunity, which is the first line of host defence mechanism and is fully functional throughout the body and life regardless of health.

  • Ficolins are similar to collectins in their structures and biologic functions with a major difference that target recognition is through fibrinogen‐like domain unlike carbohydrate recognition domain of collectins.

  • Ficolins are pattern‐recognition molecules, which are able to identify invading pathogens and abnormal cells and tissues, in addition to normal cells, which are not recognised by collectins.

  • Selected genetic mutations affect functions of ficolins and are associated with reduced host defence mechanisms.

  • Some ficolins may be a disease modifier as deficiency itself may cause no problem, whereas it may have adverse effect depending on types of disease, infection or injury.

  • Ficolins have structural and functional homology to collectins and may share and substitute functions in host defence.

Keywords: ficolin; pattern‐recognition; innate immunity; complement; inflammation

Figure 1.

Gene and protein structure of human ficolins. The exon organisation of ficolins is shown in relation to the domain structure of a single functional subunit, a trimer of ficolins. The size and distance of the exons and genes do not reflect actual sequence length.

Figure 2.

Molecular organisation of ficolins. Schematic oligomers are depicted. Detailed FBG of M‐ficolin has been analysed, although the entire molecular organisation is not yet available.

Figure 3.

Gene polymorphisms in ficolin genes. SNPs in gene sequence numbers and amino acid substitution polymorphisms in protein sequence numbers are indicated. SNPs in black, blue and red indicate no change, reduction and increase of blood levels, respectively. Fs and sp indicate flame shift and stop, respectively. Sizes of promoter, exon and intron do not reflect actual distance.

Figure 4.

Activation of complement by ficolin–MASP complex. Ficolin, which can be MBL, is loaded with MASP‐1, MASP‐2, MASP‐3, MAp44 and sMAP. It is not known that how many MASPs and MAps are associated with the ficolin. It is illustrated that MASP‐2 is able to cleave the complement factors, C2 and C4, and it may be that MASP‐1 and MASP‐3 can cleave the complement factors, B and D, leading to activation of the alternative pathway of the complement system.



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Further Reading

Garred P, Honore C, Ma YJ et al. (2009) The genetics of ficolins. Journal of Innate Immunity 2(1): 3–16.

Hummelshoj T, Nissen J, Munthe‐Fog L et al. (2011) Allelic lineages of the ficolin genes (FCNs) are passed from ancestral to descendant primates. PLoS One 6(12): e28187.

Kilpatrick DC and Chalmers JD (2012) Human L‐ficolin (ficolin‐2) and its clinical significance. Journal of Biomedicine and Biotechnology 2012: 138797.

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Takahashi, Kazue, and Thiel, Steffen(Jan 2013) Ficolins. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021209.pub2]