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Complement Receptors in Myeloid Cell Adhesion and Phagocytosis

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  • Author: Michael L. Dustin1
  • Editor: Siamon Gordon2
    Affiliations: 1: Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, The University of Oxford, Headington, OX3 7FY, United Kingdom; 2: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0034-2016
  • Received 05 May 2016 Accepted 12 September 2016 Published 04 November 2016
  • Michael L. Dustin, michael.dustin@kennedy.ox.ac.uk
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  • Abstract:

    Myeloid cells make extensive use of the complement system in the context of recruitment, phagocytosis, and other effector functions. There are several types of complement receptors on myeloid cells, including G protein-coupled receptors for localizing the source of complement activation, and three sets of type I transmembrane proteins that link complement to phagocytosis: complement receptor 1, having an extracellular domain with tandem complement regulatory repeats; complement receptors 3 and 4, which are integrin family receptors comprising heterodimers of type I transmembrane subunits; and VSIG4, a member of the Ig superfamily. This review will focus on the role of the different classes of complement receptors and how their activities are integrated in the setting of immune tolerance and inflammatory responses.

  • Citation: Dustin M. 2016. Complement Receptors in Myeloid Cell Adhesion and Phagocytosis. Microbiol Spectrum 4(6):MCHD-0034-2016. doi:10.1128/microbiolspec.MCHD-0034-2016.

Key Concept Ranking

Complement System
Immune Receptors
Immune Systems
Amino Acids


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Myeloid cells make extensive use of the complement system in the context of recruitment, phagocytosis, and other effector functions. There are several types of complement receptors on myeloid cells, including G protein-coupled receptors for localizing the source of complement activation, and three sets of type I transmembrane proteins that link complement to phagocytosis: complement receptor 1, having an extracellular domain with tandem complement regulatory repeats; complement receptors 3 and 4, which are integrin family receptors comprising heterodimers of type I transmembrane subunits; and VSIG4, a member of the Ig superfamily. This review will focus on the role of the different classes of complement receptors and how their activities are integrated in the setting of immune tolerance and inflammatory responses.

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Image of FIGURE 1

Receptors for products of C3 expressed on human macrophages. Human macrophages differentiated from CD14 monocytes with granulocyte-monocyte colony-stimulating factor express all the major complement receptors, including C3aR, C5aR, CR1, CR3, and VSIG4. The arrows with the receptor names indicate approximate binding-site location within the schematic of C3 breakdown products that are released in the production of C3a, C3b, and its covalently attached products iC3b and C3d. The upper part of the schematic is the macrophage surface and the lower part is a microbial surface bearing the complement components.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0034-2016
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Image of FIGURE 2

Schematic of the mouse and human complement receptor gene products. In the mouse, CR1 and CR2 proteins are derived from alternative splicing of the gene. Mouse CR1 and CR2 are not present on myeloid cells. In humans, the CR1 and CR2 proteins are products of different genes. Human CR1 is expressed on myeloid cells and functions in phagocytosis in addition to clearance of immune complexes bearding C3b and/or C4b. CR1 also acts as a cofactor for factor I in conversion of C3b to iC3b and, further, to C3d. Each ball is an SCR, and each group of seven repeats is referred to as an LHR.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0034-2016
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Image of FIGURE 3

Fitting integrins and complement receptors into a diffusion barrier model for the phagocytic synapse. Close contacts are inherent to immunological synapses. Fc receptors and T-cell receptors naturally fit into a 15-nm gap that generates a diffusion barrier for entry of the RO and RB splice variants of CD45 and thus tips the local kinase/phosphatase balance in favor of the kinases. Large receptors like CR3 and CR4 are too large to fit into the <15-nm space when fully extended. Active F-actin-mediated processes induced by phosphatidylinositol-3 kinase (PI-3K) signaling can work with integrins to expand close contacts in phagocytic immune synapses and increase the area from which CD45 is excluded. The relevant integrin conformations that mediate this close contact formation are not known, but may include alternative crouching conformations recently described by electron microscopy or tilted extended conformations generated by forces tangential to the membrane. CR1 function overlaps extensively with CR3/4, and thus it is possible that CR1 can also adopt conformations that facilitate close contact in an F-actin-dependent manner, despite its apparent large size. Further study is needed to understand whether CR1 also participates in close contact formation and how CR1’s structure is adapted to this task.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0034-2016
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Complement receptors involved in adhesion, migration, and phagocytosis

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0034-2016

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