Collectins

Abstract

Collectins are pattern‐recognition molecules of innate immunity and are involved in recognising pathogens and abnormal cells in an antibody‐independent manner. The name collectin is derived from the basic structure, consisting of a collagen‐like domain and a carbohydrate‐recognition domain (CRD), akin to lectins, which recognise sugars. The CRDs bind pathogen‐associated molecular patterns, which are chemical motifs exposed on the surface of pathogens and abnormal cells. Collectins are synthesised in many organs and some are circulating in blood, whereas others are localised to a tissue. Collectin genes are germinally present and therefore, their proteins are expressed at healthy state, affording an instant action. There are also a homologous protein family called ficolins, which are similar to collectins structurally and functionally. Mechanisms of actions include a direct opsonin activity, activation of complement pathways and coagulation, modulation of inflammation and adaptive immunity.

Key Concepts:

  • Collectins are molecules of innate immunity, which is the first line of host defence and is fully functional throughout the body and the life regardless of health.

  • Collectins are pattern‐recognition molecules, which are able to identify invading pathogens and abnormal cells and tissues.

  • Selected genetic mutations affect functions of collectins and are associated with reduced host defence mechanisms and developmental disorder.

  • Some collectins are disease modifier, as deficiency itself may cause no problem whereas it may have adverse effect depending on type of disease, infection or sterile injury.

  • Collectins have homology to ficolins structurally and functionally, and may share and substitute functions in host defence.

Keywords: pattern‐recognition; innate immunity; mannose‐binding lectin; surfactant proteins; collectin; coagulation; complement; pathogens

Figure 1.

Innate immune system. The illustration shows examples of innate immune cells in tissues, such as resident cells in all tissues, keratinocytes of the skin, alveoli epithelial cells in the lung, mucosal epithelial cells in the small intestine. The latter synthesises pattern recognition molecules. Blood vessels are also important innate immune organ, including, smooth muscle and endothelial cells. There are circulating innate immune cells, including monocytes, neutrophils, lymphocytes and platelets. These circulating cells and molecules may reach regions at the site of pathogen invasion and injury.

Figure 2.

Gene and protein structure of human collectins. Exon organisations of collectins are compared against a polypeptide chain and a single subunit, a trimer of the polypeptide chain. MBL, SP‐A and SP‐D are closely located on chromosome 10q. CLP‐1 is the membrane‐bound form, whereas others are typical soluble form as illustrated below the gene structures. Size and distance of exons and genes do not reflect actual distance of conformation.

Figure 3.

Molecular organisation of collectins. Oligomeric molecular forms are compared. Domain encoding exons are coloured, according to protein domains.

Figure 4.

Carbohydrate‐recognition patterns for MBL recognition. (a) Atomic pattern of equatorial hydroxyl groups at positions 3 and 4 that is recognised by an individual carbohydrate‐recognition domain (micropattern). (b) Molecular pattern recognised by MBL oligomers (macropattern), for illustrative purpose here seen with a dimer of MBL, which is actually seldom found.

Figure 5.

Activation of complement by MBL–MASP complex. MBL, which can be also ficolins, is loaded with MASP‐1, MASP‐2, MASP‐3, MAp44 and sMAP. It is not known how many MASPs and MAps are actually found on the MBL molecule. It is illustrated that MASP‐2 is able to cleave the complement factors C2 and C4, and that it may be that MASP‐1 and MASP‐3 can cleave the complement factor B and D leading to activation of the alternative pathway of complement system.

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Further Reading

Matthijsen RA, Derikx JP, Steffensen R et al. (2009) Mannose‐binding lectin null alleles are associated with preserved epithelial cell integrity following intestinal ischemia reperfusion in man. Molecular Immunology 46(11–12): 2244–2248.

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How to Cite close
Thiel, Steffen, and Takahashi, Kazue(Jan 2013) Collectins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003659.pub3]