Human L-Ficolin (Ficolin-2) and Its Clinical Significance

Abstract

<jats:p>Human L-ficolin (P35, ficolin-2) is synthesised in the liver and secreted into the bloodstream where it is one of the major pattern recognition molecules of plasma/serum. Like other ficolins, it consists of a collagen-like tail region linked to a fibrinogen-related globular head; a basic triplet subunit arises via a collagen-like triple helix, and this then forms higher multimers (typically a 12-mer, Mr 400K). Unlike other ficolins, it has a complex set of binding sites arranged within an internal cleft enabling it to recognise a variety of molecular patterns including acetylated sugars and certain 1,3-<jats:italic>β</jats:italic>-glucans. It is one of the few molecules known to activate the lectin pathway of complement. Recently, some disease association studies (at either the DNA or protein level) have implicated L-ficolin in innate immunity, where it might cooperate with pentraxins and collectins. Emerging lines of evidence point to a role for L-ficolin in respiratory immunity, where its affinity for<jats:italic>Pseudomonas aeruginosa</jats:italic>could be significant.</jats:p>

The Lack of Association between <b><i>FCN2</i></b> Gene Promoter Region Polymorphisms and Dental Caries in Polish Children

“…Ficolin-2 is able to bind to distinct pathogenassociated molecular patterns, such as carbohydrates (GlcNAc), lipoteichoic acid and acetylated groups, and then facilitating phagocytosis and activating complement [Munthe-Fog et al, 2007]. Ficolin-2 was found to have a broad profile towards the Gram-negative bacteria, such as Salmonella Typhimurium , Escherichia coli , Pseudomonas aeruginosa , as well as to Gram-positive bacteria, including Staphylococcus aureus and streptococci [Kilpatrick and Chalmers, 2012;Hummelshøj et al, 2012]. Thirty-six polymorphisms in the gene encoding ficolin-2 ( FCN2 ) have been detected [Garred et al, 2010]; of them only 7 SNPs appear to be of potential importance [Kilpatrick and Chalmers, 2012].…”

“…Ficolin-2 was found to have a broad profile towards the Gram-negative bacteria, such as Salmonella Typhimurium , Escherichia coli , Pseudomonas aeruginosa , as well as to Gram-positive bacteria, including Staphylococcus aureus and streptococci [Kilpatrick and Chalmers, 2012;Hummelshøj et al, 2012]. Thirty-six polymorphisms in the gene encoding ficolin-2 ( FCN2 ) have been detected [Garred et al, 2010]; of them only 7 SNPs appear to be of potential importance [Kilpatrick and Chalmers, 2012]. Three SNPs in the promoter region of the FCN2 gene (at positions -986, -602, and -4) are associated with variation in serum concentration of ficolin-2 [Hummelshøj et al, 2005;Garred et al, 2010].…”

Commercially Available Complement Component-Depleted Sera Are Unexpectedly Codepleted of Ficolin-2

“…This family of proteins functions as pattern recognition molecules with an affinity for acetylated ligands (1). Ficolin-2 has been recently shown to be important during pneumococcal pathogenesis (2)(3)(4) and is known to bind to many other significant human pathogens (2,5,6). Moreover, ficolin-2 and -3 have been implicated in many different disease pathologies, such as transplant reperfusion injury (7), clearance of apoptotic cells (8,9), and even preeclampsia (10).…”

The prevalence of the variants of the L-ficolin gene (FCN2) in the arctic populations of East Siberia

“…Currently, only a few molecules known to activate the lectin pathway of complement activation: the human ficolins and the collectins (mannose-binding lectin (MBL), collectin liver-1, and collectin kidney-1). All these molecules are capable to recognise surface-linked carbohydrates or acetyl groups on pathogens (Kilpatrick and Chalmers 2012;Troldborg et al 2017). It has been supposed that individuals with combined MBL2 and ficolins deficiency may be at risk to morbidity (Bjarnadottir et al 2016).…”