CD163-L1 is an endocytic macrophage protein strongly regulated by mediators in the inflammatory response.

CD163-L1 belongs to the group B scavenger receptor cysteine-rich family of proteins, where the CD163-L1 gene arose by duplication of the gene encoding the hemoglobin scavenger receptor CD163 in late evolution. The current data demonstrate that CD163-L1 is highly expressed and colocalizes with CD163 on large subsets of macrophages, but in contrast to CD163 the expression is low or absent in monocytes and in alveolar macrophages, glia, and Kupffer cells. The expression of CD163-L1 increases when cultured monocytes are M-CSF stimulated to macrophages, and the expression is further increased by the acute-phase mediator IL-6 and the anti-inflammatory mediator IL-10 but is suppressed by the proinflammatory mediators IL-4, IL-13, TNF-α, and LPS/IFN-γ. Furthermore, we show that CD163-L1 is an endocytic receptor, which internalizes independently of cross-linking through a clathrin-mediated pathway. Two cytoplasmic splice variants of CD163-L1 are differentially expressed and have different subcellular distribution patterns. Despite its many similarities to CD163, CD163-L1 does not possess measurable affinity for CD163 ligands such as the haptoglobin-hemoglobin complex or various bacteria. In conclusion, CD163-L1 exhibits similarity to CD163 in terms of structure and regulated expression in cultured monocytes but shows clear differences compared with the known CD163 ligand preferences and expression pattern in the pool of tissue macrophages. We postulate that CD163-L1 functions as a scavenger receptor for one or several ligands that might have a role in resolution of inflammation.

Cloning and characterization of SCART1, a novel scavenger receptor cysteine-rich type I transmembrane molecule.

We have cloned and characterized a novel murine transmembrane molecule, mSCART1 belonging to the scavenger receptor cysteine-rich superfamily. The cDNA encodes a polypeptide chain of 989 amino acids, organized as a type I transmembrane protein that contains eight extracellular SRCR domains followed by a transmembrane region and a cytoplasmic domain. The cytoplasmic domain contains two putative src kinase consensus substrate sequences, three additional potential phosphorylation sites, and two potential internalization motifs. Two possible secreted forms that lack the transmembrane region arise by alternative splicing. The murine SCART1 gene maps to chromosome 7 band F5 and the analysis of the genomic organization showed that the gene spans 12.86 kb and contains 14 exons. Quantitative real-time PCR analyses on murine tissues showed high mSCART1 mRNA expression in the lymph node, the trachea, and the lung, and low expression was found in the thymus, the spleen, the skin, and in tissues throughout the gastrointestinal tract. Comparative studies of the domain organization as well as the cytoplasmic domain of mSCART1 with the other members of the SRCR superfamily show that mSCART1 is highly related to the WC1 family of the SRCR superfamily. Finally, a novel human scavenger receptor cysteine-rich molecule with high homology to mSCART1 was identified by searching in the human genomic databases using the mSCART1 cDNA sequence.

The Scavenger Receptor Cysteine-Rich (SRCR) domain: an ancient and highly conserved protein module of the innate immune system.

The Scavenger Receptor Cysteine-Rich (SRCR) domain is an ancient and highly conserved protein module of ~100-110 amino acids, which defines a superfamily (SRCR-SF) of either soluble or membrane-bound receptors expressed by hematopoietic and nonhematopoietic cells, at either embryonic or adult stages. The existence of two types of SRCR domains allows the division of the SRCR-SF into two groups. Members of group A contain SRCR domains with 6 cysteine residues and are encoded by two exons, whereas those of group B usually contain 8 cysteines and are encoded by a single exon. Group A members usually present as multidomain mosaic proteins containing single SRCR domains associated to other functional domains, such as enzymatic (protease) domains or collagenous regions. On the contrary, group B members generally present as proteins exclusively composed of tandem repeats of SRCR domains, with or without the presence of CUB and ZP domains thought to be involved in oligomerization but never associated to protease domains. Representatives of either group are found in different animal species, from low invertebrates (sponges) to high vertebrates (mammals). Although no unifying function has been defined for SRCR-SF members, accumulated data, together with the high degree of structural and phylogenetic conservation of SRCR domains indicates that they might subserve basic homeostatic functions, including innate immune defense.