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Chemokine Receptors: Monocyte

Isabel Crane, University of Aberdeen, UK

Chemokine receptors are G-protein coupled receptors (GPCRs) which enable a cell to respond to its chemokine ligand(s). Binding to chemokine induces a conformational change in the receptor which leads to intracellular signalling, resulting in chemotactic movement, increased avidity and affinity of integrins, and, in some cases, cell activation. The interaction between chemokine receptors of a cell and chemokine is fundamental to the recruitment of the cell to the appropriate site for action.

Monocytes, derived from myeloid progenitors in the bone marrow, circulate in the blood.  They are important for an inflammatory response, differentiating into macrophages or dendritic cells (DC) under certain circumstances. Two major subpopulations of monocytes have been identified in mice on the basis of their expression of Ly6C and the chemokine receptors, CCR2 and CX3CR1. The largest population under steady state conditions is Ly6Chi, CCR2hi, CX3CR1low, and the second Ly6Clow, CCR2low, CX3CR1hi. These correspond to populations found in human blood, CD14++, CD16, CCR2hi, CX3CR1low (classical), and CD14+, CD16++, CX3CR1hi, CCR2low (non-classical) respectively. However, in humans a third subset can be identified, CD14++, CD16+, CX3CR1hi, CCR2low (intermediate).

In mice, the CCR2hi subset is often referred to as inflammatory and is usually the predominant subset recruited at an inflammatory site.  However, evidence has shown that CCR2 may be more important for the release of CCR2hi monocytes from the bone marrow in response to CCL2 than for entry into inflammatory sites (Figure 1). CCR2hi monocytes once in tissue will differentiate into inflammatory macrophages or DC.

Chemokine receptors - monocyte - Figure 1
Figure 1. CCR2 is important for monocyte release from the bone marrow. Figure courtesy of F.J. Ward

Chemokine receptors - monocyte - Figure 2
Figure 2. Crawling CX3CR1hi monocytes and circulating CCR2hi monocytes are both recruited to an inflammatory site. Figure courtesy of F.J. Ward

CX3CR1hi monocytes have been shown to adhere and crawl along the luminal side of the vascular endothelium in a CX3CR1- and LFA-1-dependent manner, slowly but efficiently scanning for any inflammatory stimulus. If a stimulus is detected they are very rapidly recruited into the inflammatory site in advance of CCR2hi monocytes (Figure 2). It is thought that they may differentiate into macrophages with a role in wound healing and repair. Monocyte recruitment may also be influenced by expression of other chemokine receptors such as CCR1 and CCR5 and the relative importance of the chemokine receptors is likely to depend upon the particular microenvironment prevailing at the inflammatory site.

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