The rat macrophage scavenger receptor CD163: Expression, regulation and role in inflammatory mediator production
Introduction
Macrophages play important roles in normal and during various pathological conditions, such as (autoimmune) inflammation, infection, atherosclerosis and cancer. The major activities of , including phagocytosis and the production of inflammatory mediators, are controlled by surface receptors.
The surface glycoprotein CD163 is a member of the scavenger receptor cysteine-rich group B (SRCR-B) family and human CD163 has been shown to function as a scavenger receptor for hemoglobin–haptoglobin complexes and this may contribute to the clearance of toxic-free hemoglobin from the circulation and tissues (Law et al., 1993; Kristiansen et al., 2001). Engagement of human CD163 also results in the production of pro- and anti-inflammatory cytokines suggesting a potential role in host defense and/or inflammation (Van den Heuvel et al., 1999; Philippidis et al., 2004; Ritter et al., 2000). Human CD163 is expressed on tissue and on a subset of monocytes (Van den Heuvel et al., 1999; Radzun et al., 1987). Expression on monocytes can be upregulated by glucocorticoids and anti-inflammatory cytokines, such as IL10 (Van den Heuvel et al., 1999; Hogger et al., 1998; Buechler et al., 2000). Consequently, CD163 has been indicated as a possible marker for so-called alternatively activated , which have been suggested to possess immune-suppressive activity (Gordon, 2003; Mosser, 2002; Verreck et al., 2006). Thus far, little is known about the expression and function of CD163 in other species, such as rodents. We have recently demonstrated by purification and peptide sequencing that the rat ED2 antigen represents the rat ortholog of CD163 (Fabriek et al., submitted). Our previous analysis has demonstrated that rat CD163/ED2-antigen is expressed on subsets of tissue (Dijkstra et al., 1985; Damoiseaux et al., 1989; Barbe et al., 1990).
In the present study, we extend these findings and confirm that rat CD163 is a marker for most mature tissue . Furthermore, we evaluate the regulation of rat CD163 by glucocorticoids and IL4. Finally, we provide evidence that rat CD163 upon ligation can trigger the production of pro-inflammatory mediators in .
Section snippets
Animals
Male Wistar rats, between 7 and 12 weeks of age, were obtained from CPB-Harlan (Zeist, The Netherlands). Animals were kept under routine laboratory conditions and allowed free access to food and water. Microbiological status of the animals was according to FELASA recommendations.
Monoclonal antibodies (mAbs)
mAbs ED2 (IgG1, Dijkstra et al., 1985) and BF5 (IgG1, against human CD4: a generous gift of Dr. J. Wijdenes, Diaclone Laboratories, Besançon, France) were purified from cell culture supernatants from hybridoma cells
Rat CD163 is selectively expressed by mature tissue
Previous studies have shown that ED2 specifically recognizes a subset of mature tissue in the rat, but not bone marrow macrophage progenitors, monocytes, granulocytes or dendritic cells (Dijkstra et al., 1985; Dijkstra and Damoiseaux, 1993; Damoiseaux et al., 1989). In this study, we extend the tissue distribution analysis of the CD163 antigen by analyzing additional tissues and isolated cell populations (Fig. 1 and Table 1). The main conclusion is that rat CD163 is exclusively expressed by
Discussion
The ED2 mAb is widely used as a marker for rat , but the nature of the surface glycoprotein has remained elusive. Recently, we have established the identity of ED2 antigen by microsequencing and demonstrated that it is the rat ortholog of CD163 (Fabriek et al., in preparation). The human and mouse CD163 molecules had previously been cloned and sequenced (Law et al., 1993; Hogger et al., 1998, Schaer et al., 2001). The extracellular region of CD163 is composed of nine SRCR domains, and CD163
Acknowledgements
We thank Don W. Mason for his generous gift of rat recombinant IL-4, and Peter H. Van der Meide for his generous gifts of IFN- and IFN-. We are also grateful to Ed A. Döpp and Priscilla Heijnen, for hybridoma maintenance and antibody production.
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