Ficolin

Structure

Ficolins (Fi+Col+Lin) are a group of oligomeric lectins with N-terminal collagen-like domain and a C-terminal fibrinogen-like domain. The primary ficolin structure contains 288 amino acids. The combination of collagen-like and fibrinogen-like domain allows the protein to form a basic subunit containing a triple helical tail and a trio of globural heads.[1]

Ficolins are produced in the liver by hepatocytes and in the lung by alveolar cells type II, neutrophils and monocytes.[2]

Role in Innate Immunity

We now know, that innate immune recognition mechanisms are sophisticated and highly specific. The exocrine secretion provides a variety of soluble factors that are able to protect the body from potential pathogens.[3]

Together with pentraxins, collectins and C1q molecules they are the soluble pattern-recognition molecules (PRMs) which play an important role in humoral innate immunity.[3] Ficolins recognise the carbohydrates structures on pathogens surfaces as the pattern-recognition molecule and activate the lectin pathway of the complement cascade.[2][4] When the pattern-recognition molecules (PRMs) bind to the ligand, it initiates the proteolytic complement cascade. Serine proteases then cleave a number of soluable complement proteins leading to complement activation, such as opsonisation, generation of proinflammatory mediators, and cell lysis.[5]

Collectins and ficolins are also called collagenous lectins. The collectin family is calcium-dependent proteins. In contrast, the ficolin family does not bind to pattern-recognition molecules in a calcium-dependent way.[2]

Types of Ficolin

Three ficolins have been identified in humans:

  1. M-ficolin (FCN1), monocyte ficolin
  2. L-ficolin (FCN2), liver ficolin
  3. H-ficolin (FCN3), hakata antigen.[2][1]

Ficolin-1 and ficolin-2 are encoded be a gene localised on chromosome 9 (9q34) and they share approximately 80% identity in amino sequence. Whereas, ficolin-3 is encoded by chromosome 1 and therefore it has only about 50% identity with the other two ficolins.[1] A cross-reactivity of the ficolins in human serum has been observed.[5]

Clinical References

The concentration of ficolins in healthy serum is between 3 and 5 μg/mL.[1]

As Ficolin-2 and 3 are expressed by hepatocytes, their levels decrease in advanced liver diseases like cirrhosis. Low ficolin levels contribute to cirrhosis-associated immune dysfunction.[6]

Immunologist Jeak L. Ding and her team found that natural IgG (nIgG; a non-specific immunoglobulin of adaptive immunity) is not quiescent, but plays a crucial role in immediate immune defense by collaborating with ficolin (an innate immune protein).

References

  1. 1 2 3 4 Kilpatrick, David C.; Chalmers, James D. (2012). "Human L-Ficolin (Ficolin-2) and Its Clinical Significance". Journal of Biomedicine and Biotechnology. 2012: 1–10. doi:10.1155/2012/138797. ISSN 1110-7243.
  2. 1 2 3 4 Matsushita, Misao (2018), "Ficolins", The Complement FactsBook, Elsevier, pp. 45–56, retrieved 2022-02-06
  3. 1 2 Hajishengallis, George; Russell, Michael W. (2015), "Innate Humoral Defense Factors", Mucosal Immunology, Elsevier, pp. 251–270, retrieved 2022-02-06
  4. ↑ Endo, Yuichi; Matsushita, Misao; Fujita, Teizo (June 2007). "Role of ficolin in innate immunity and its molecular basis". Immunobiology. 212 (4–5): 371–379. doi:10.1016/j.imbio.2006.11.014. ISSN 0171-2985.
  5. 1 2 Jarlhelt, Ida; Pilely, Katrine; Clausen, Jytte Bryde; Skjoedt, Mikkel-Ole; Bayarri-Olmos, Rafael; Garred, Peter (2020-02-24). "Circulating Ficolin-2 and Ficolin-3 Form Heterocomplexes". The Journal of Immunology. 204 (7): 1919–1928. doi:10.4049/jimmunol.1900694. ISSN 0022-1767.
  6. ↑ Foldi, Ildiko; Tornai, Tamas; Tornai, David; Sipeki, Nora; Vitalis, Zsuzsanna; Tornai, Istvan; Dinya, Tamas; Antal‐Szalmas, Peter; Papp, Maria (2017). "Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections". Liver International. 37 (7): 1023–1031. doi:10.1111/liv.13368. hdl:2437/234045. ISSN 1478-3231.
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