Complement Receptors and Their Role in Leukocyte Recruitment and Phagocytosis.

Sofie Vandendriessche,Seppe Cambier,Pedro E Marques,Paul Proost

doi:10.3389/fcell.2021.624025

Sofie Vandendriessche, Seppe Cambier + Show 2 more

Open Access

https://doi.org/10.3389/fcell.2021.624025

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Abstract

The complement system is deeply embedded in our physiology and immunity. Complement activation generates a multitude of molecules that converge simultaneously on the opsonization of a target for phagocytosis and activation of the immune system via soluble anaphylatoxins. This response is used to control microorganisms and to remove dead cells, but also plays a major role in stimulating the adaptive immune response and the regeneration of injured tissues. Many of these effects inherently depend on complement receptors expressed on leukocytes and parenchymal cells, which, by recognizing complement-derived molecules, promote leukocyte recruitment, phagocytosis of microorganisms and clearance of immune complexes. Here, the plethora of information on the role of complement receptors will be reviewed, including an analysis of how this functionally and structurally diverse group of molecules acts jointly to exert the full extent of complement regulation of homeostasis.

Highlights

TO THE COMPLEMENT SYSTEMEvolution of ComplementThe mammalian complement system comprises more than 50 fluid and membrane-associated proteins that control multiple aspects of physiology and immunity (Hajishengallis et al, 2017)
Increased serum levels of antinuclear Abs and anti-DNA Abs have been found in Cr2null mice (Wu et al, 2002). These results indicate a role for Complement Receptor 2 (CR2) in systemic lupus erythematosus (SLE) pathogenesis, one must keep in mind that these were obtained in mice, in which a single gene encodes for both Complement Receptor 1 (CR1) and CR2
Activation of anaphylatoxin- and other G protein-coupled receptor (GPCR) during rolling is essential for further leukocyte transmigration into inflamed tissues, which is mediated by activation of CR3, CR4 and other integrins

Summary

INTRODUCTION

The mammalian complement system comprises more than 50 fluid and membrane-associated proteins that control multiple aspects of physiology and immunity (Hajishengallis et al, 2017). In response to microbial infection or tissue damage, release of pro-inflammatory mediators increases the blood flow and the expression of endothelial adhesion molecules This allows leukocytes to increase rolling along the luminal side of the activated endothelium, mediated by weak and transient selectinglycoprotein interactions (McEver, 2002). [2] This allows interaction of leukocyte GPCRs (including C5aR and other chemoattractant receptors) with chemoattractant molecules, produced by tissue-resident cells in response to and forming a chemotactic gradient toward the inflammatory trigger This results in inside-out activation of integrins, changing their global conformation from a bent non-activated conformation to an extended, activated conformation with higher affinity for the integrin ligands ICAM-1, ICAM-2 and VCAM-1, which belong to the immunoglobulin (Ig) superfamily adhesion molecules [3]. In LAD-II, mutations in a specific GDP-fucose transporter result in impaired synthesis of selectin glycoprotein ligands, impairing the leukocyte rolling and eventually resulting in impaired leukocyte extravasation (Sturla et al, 2001)

Introduction to Phagocytosis

Findings

CONCLUSION