Ficolins are pattern recognition receptors that bind to acetyl groups present in the

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

s of bacterial surfaces and mediate activation of the

lectin pathway The lectin pathway or MBL pathway is a type of cascade reaction in the complement system, similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated comple ...

of the complement cascade.

Structure

Ficolins (Fi+Col+Lin) are a group of

oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...

lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar Moiety (chemistry), groups that are part of other molecules, so cause agglutination (biology), agglutination of particular cells or precipitation of glycoconjugates an ...

s 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

hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bi ...

s and in the lung by alveolar cells type II,

neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...

s and

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...

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 The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...

. Ficolins recognise

structures on pathogens' surfaces as their

pathogen-associated molecular pattern Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes, but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both p ...

(PAMP) and activate the lectin pathway of the complement cascade. Specifically, ficolins bind to

acetyl In organic chemistry, an acetyl group is a functional group denoted by the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, an acetyl grou ...

groups present in certain bacterial molecules, such as N-acetylglucosamine, a component of

peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating ...

in the bacterial cell wall. When ficolins bind to their PAMP

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

s 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 protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Serin ...

s 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 collectin 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 Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...

. 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).

References

{{Complement system Ficolins Blood proteins Human proteins Lectins