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The Mannose-Binding Lectin (MBL) Route for Activation of Complement

  • Conference paper
Glycobiology and Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 535))

Abstract

The human complement system consists of more than thirty proteins, which are either soluble in body fluids, especially the blood plasma, or bound to cell membranes (for a recent overview, see Morley and Walport, 2000). These complement components are organized in three activating pathways and one terminal pathway (Figure 1). Activation of the system occurs via the classical, alternative, or lectin pathway, on recognition of particulate materials by binding of complement proteins to charge or carbohydrate arrays (Sim, 1993). This eventually results in the assembly of unstable protease complexes called the C3 convertases, C4b2a and C3bBb, which activate the central complement component C3. The major fragment of activated C3, C3b, binds covalently to complement-activating surfaces, and is responsible for initiating most of the effector mechanisms of the system. C3b and its cleaved form, iC3b, act as opsonins, enhancing phagocytosis of the complement-activating particles, while C3b can also combine with the C3 convertases to form C5 convertases and initiate the assembly of the membrane attack complex (MAC) which can insert into a lipid bilayer on the target cell, causing cell lysis. The minor fragment of activated C3, C3a, is an anaphylatoxin, and like the other anaphylatoxins of the complement system, C4a and C5a, it can mediate inflammatory responses, including smooth muscle contraction and increased vascular permeability. Therefore, the complement system recognizes and targets potentially harmful molecules or cells for destruction by opsonisation, cell lysis, or induction of the inflammatory response. In addition, other effector mechanisms of the system have been reported, which include solubilization of immune complexes and targeting of antigen to B-cells (Dempsey et al., 1996) and to dendritic cells. Excessive or inappropriate activation of complement may damage host tissue, and the system is under elaborate control by regulatory proteins.

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  1. MRC Immunochemistry Unit Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    M. Kojima, J. S. Presanis & R. B. Sim

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Kojima, M., Presanis, J.S., Sim, R.B. (2003). The Mannose-Binding Lectin (MBL) Route for Activation of Complement. In: Axford, J.S. (eds) Glycobiology and Medicine. Advances in Experimental Medicine and Biology, vol 535. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0065-0_15

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