Ficolin
Family of proteins
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Through Carbohydrate and Ligand (biochemistry)
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 globular heads.
Ficolins are produced in the liver by hepatocytes and in the lung by alveolar cells type II, neutrophils and monocytes.
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Role in innate immunity
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. Ficolins recognise carbohydrate structures on pathogens' surfaces as their pathogen-associated molecular pattern (PAMP) and activate the lectin pathway of the complement cascade. Specifically, ficolins bind to acetyl groups present in certain bacterial molecules, such as N-acetylglucosamine, a component of peptidoglycan in the bacterial cell wall. 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.
Collectins and ficolins are also called collagenous lectins. The collection family constitutes calcium-dependent proteins. In contrast, the ficolin family does not bind to PAMPs in a calcium-dependent way.
Types of ficolin
Three ficolins have been identified in humans:
- M-ficolin (FCN1), monocyte ficolin
- L-ficolin (FCN2), liver ficolin
- 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.
Clinical references
The concentration of ficolins in healthy serum is between 3 and 5 μg/mL.
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.
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).