ficolin

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 globular heads.

Ficolins are produced in the liver by hepatocytes and in the lung by alveolar cells type II, neutrophils and monocytes.{{cite book|last=Matsushita|first=Misao|chapter=Chapter 5 - Ficolins|date=2018|doi=10.1016/B978-0-12-810420-0.00005-5|title=The Complement FactsBook|editor-last1=Barnum|editor-first1=Scott R.|editor-last2=Schein|editor-first2=Theresa N.|edition=Second|pages=45–56|publisher=Elsevier|isbn=978-0-12-810420-0}}

We now know that innate immune recognition mechanisms are sophisticated. Exocrine secretions provide a variety of soluble factors that are able to protect the body from potential pathogens.

Together with pentraxins, collectins and C1q molecules, ficolins constitute the soluble pattern-recognition molecules (PRMs) which play an important role in humoral innate immunity.{{cite book|last1=Hajishengallis|first1=George|chapter=Chapter 15 - Innate Humoral Defense Factors|date=2015|doi=10.1016/b978-0-12-415847-4.00015-x|doi-access=free|title=Mucosal Immunology|edition=Fourth|pages=251–270|publisher=Elsevier|last2=Russell|first2=Michael W.|editor-last1=Mestecky|editor-first1=Jiri|editor-last2=Strober|editor-first2=Warren|editor-last3=Russell|editor-first3=Michael W.|editor-last4=Kelsall|editor-first4=Brian L.|editor-last5=Cheroutre|editor-first5=Hilde|editor-last6=Lambrecht|editor-first6=Bart N.|isbn=978-0-12-415847-4}} Ficolins recognise carbohydrate structures on pathogens' surfaces as their pathogen-associated molecular pattern (PAMP) and activate the lectin pathway of the complement cascade.{{Cite journal|last1=Endo|first1=Yuichi|last2=Matsushita|first2=Misao|last3=Fujita|first3=Teizo|date=June 2007|title=Role of ficolin in innate immunity and its molecular basis|url=http://dx.doi.org/10.1016/j.imbio.2006.11.014|journal=Immunobiology|volume=212|issue=4–5|pages=371–379|doi=10.1016/j.imbio.2006.11.014|pmid=17544822 |issn=0171-2985|doi-access=free}} Specifically, ficolins bind to acetyl groups present in certain bacterial molecules, such as N-acetylglucosamine, a component of peptidoglycan in the bacterial cell wall.{{cite journal |last1=Krarup |first1=Anders |last2=Thiel |first2=Steffen |last3=Hansen |first3=Annette |last4=Fujita |first4=Teizo |last5=Jensenius |first5=Jens C. |title=L-ficolin Is a Pattern Recognition Molecule Specific for Acetyl Groups |year=2004 |journal=Journal of Biological Chemistry |volume=279 |issue=46 |pages=47513–47519 |doi=10.1074/jbc.M407161200 |pmid=15331601 |doi-access=free}} When ficolins bind to their PAMP ligands by their C-terminal fibrinogen-like domain, they initiate the proteolytic complement cascade, facilitated by the mannose-binding protein-associated serine proteases (MASPs) that ficolins are associated to and co-circulate with. Serine proteases then cleave a number of soluble complement proteins leading to complement activation, opsonisation, generation of proinflammatory mediators, and cell lysis.{{Cite journal|last1=Jarlhelt|first1=Ida|last2=Pilely|first2=Katrine|last3=Clausen|first3=Jytte Bryde|last4=Skjoedt|first4=Mikkel-Ole|last5=Bayarri-Olmos|first5=Rafael|last6=Garred|first6=Peter|date=2020-02-24|title=Circulating Ficolin-2 and Ficolin-3 Form Heterocomplexes|journal=The Journal of Immunology|volume=204|issue=7|pages=1919–1928|doi=10.4049/jimmunol.1900694|pmid=32094208 |s2cid=211477247 |issn=0022-1767|doi-access=free}}

Collectins and ficolins are also called collagenous lectins. The collectin family constitutes calcium-dependent proteins. In contrast, the ficolin family does not bind to PAMPs in a calcium-dependent way.

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.

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. A cross-reactivity of the ficolins in human serum has been observed.

The concentration of ficolins in healthy serum is between 3 and 5 μg/mL.{{Cite journal|last1=Kilpatrick|first1=David C.|last2=Chalmers|first2=James D.|date=2012|title=Human L-Ficolin (Ficolin-2) and Its Clinical Significance|journal=Journal of Biomedicine and Biotechnology|volume=2012|page=138797 |doi=10.1155/2012/138797|pmid=22500076 |pmc=3303570 |issn=1110-7243|doi-access=free }}

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.{{Cite journal|last1=Foldi|first1=Ildiko|last2=Tornai|first2=Tamas|last3=Tornai|first3=David|last4=Sipeki|first4=Nora|last5=Vitalis|first5=Zsuzsanna|last6=Tornai|first6=Istvan|last7=Dinya|first7=Tamas|last8=Antal-Szalmas|first8=Peter|last9=Papp|first9=Maria|date=2017|title=Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.13368|journal=Liver International|language=en|volume=37|issue=7|pages=1023–1031|doi=10.1111/liv.13368|pmid=28109038 |issn=1478-3231|hdl=2437/234045|s2cid=4724419 |hdl-access=free}}

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).{{cite journal |last1=Panda |first1=Saswati |last2=Ding |first2=Jeak L. |title=Natural Antibodies Bridge Innate and Adaptive Immunity |journal=The Journal of Immunology |volume=194 |issue=1 |pages=13–20 |year=2015 |doi=10.4049/jimmunol.1400844 |pmid=25527792 |doi-access=free}}

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Category:Ficolins

Category:Blood proteins

Category:Human proteins

Category:Lectins