Structural and functional diversity of collectins and ficolins and their relationship to disease

Abstract

Pattern recognition molecules are sensors for the innate immune system and trigger a number of pathophysiological functions after interaction with the corresponding ligands on microorganisms or altered mammalian cells. Of those pattern recognition molecules used by the complement system, collagen-like lectins (collectins) are an important subcomponent. Whereas the best known of these collectins, mannose-binding lectin, largely occurs as a circulating protein following production by hepatocytes, the most recently described collectins exhibit strong local biosynthesis. This local production and release of soluble collectin molecules appear to serve local tissue functions at extravascular sites, including a developmental function. In this article, we focus on the characteristics of collectin-11 (CL-11 or CL-K1), whose ubiquitous expression and multiple activities likely reflect a wide biological relevance. Collectin-11 appears to behave as an acute phase protein whose production associated with metabolic and physical stress results in locally targeted inflammation and tissue cell death. Early results indicate the importance of fucosylated ligand marking the injured cells targeted by collectin-11, and we suggest that further characterisation of this and related ligands will lead to better understanding of pathophysiological significance and exploitation for clinical benefit.

Keywords: Collectin-11; Glycans; Innate immunity; Lectin pathway.

Fig. 1

Roles of lectin pathway PRRs in multiple situations and important processes. Upon presentation of a number of different situations; cell stress, bacterial, viral or fungal invasion and apoptotic cells, the PRRs of the lectin pathway bind to substrates and through MASPs cause lectin pathway mediated cleavage of C3. This stimulates inflammation, enhances antigen presentation and T and B cell responses, opsonisation, parenchymal injury and cell death. In addition, PRRs of the lectin pathway have roles in the clotting cascade and MASPs themselves can aid in the regulation of certain cellular and developmental pathways. PRR pattern recognition receptor, LP lectin pathway, MASP MBL-associated serine protease, Ag antigen, LTA lipoteichoic acid. Note that the binding ligand for CL-11 on mammalian cells is represented as a monosaccharide, when in reality it forms part of complex polysaccharides