The macrophage scavenger receptor CD163: endocytic properties of cytoplasmic tail variants

Abstract: CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are substantially expressed in blood, liver, and spleen, and the short tail variant is the predominant mRNA species. Using cell trans-fectants in which cDNA encoding the CD163 vari-ants was inserted at the same site in the genome, we evaluated the expression and endocytic properties of the tail variants. Ligand uptake analysis showed that cells expressing the CD163 short tail variant exhibited a higher capacity for ligand endocytosis than cells expressing the CD163 long tail variants. The difference in endocytic activity was explained by confocal microscopic analysis, showing marked deviations in subcellular distribution. Surface ex-pression was far most pronounced for the CD163 short tail variant, whereas the long tail variants were most abundant in the Golgi region/endo-somes. Mutational change of a putative signal for endocytosis (Tyr-Arg-Glu-Met), present in a com-mon part of the cytoplasmic tail of the variants, almost completely inactivated the endocytic activ-ity of the short tail variant. In conclusion, the three physiological tail variants of CD163 may contrib-ute to Hp-Hb endocytosis by means of the common ligand-binding region and endocytic signal. How-ever, the high mRNA expression level and rela-tively high endocytic capacity of the short tail vari-ant suggest that it accounts for the majority of Hp-Hb uptake from the circulation, whereas the long tail variants may have yet-unknown intracel-lular roles. J. Leukoc. Biol. 79: 837–845; 2006. Key Words: haptoglobin haemoglobin endocytic signal trans-fectio