Cross‐linking of FcγR triggers shedding of the hemoglobin‐haptoglobin scavenger receptor CD163

CD163, the hemoglobin (Hb)-hapto- globin scavenger receptor, is a monocyte/macro- phage-restricted member of the scavenger recep- tor, cysteine-rich family of proteins. In addition to being expressed on the cell surface, a soluble form of CD163 has also been reported. Like tumor ne- crosis factor (TNF-), surface CD163 is proteo- lytically cleaved from the plasma membrane in re- sponse to lipopolysaccharide (LPS) stimulation. As cross-linking of the Fc receptor (FcR) is simi- larly known to induce TNF- shedding, the effect of FcR stimulation on CD163 shedding was inves- tigated. We found that FcR stimulation resulted in a rapid release of surface CD163 into the super- natant that was blocked by inhibitors of protein kinase C and tyrosine kinases. Although LPS and FcR stimulation in short-term cultures sup- pressed CD163 mRNA expression, long-term cul- tures of monocytes treated with LPS—but not with aF cR cross-linking reagent—resulted in an inter- leukin-10-dependent recovery of surface CD163 expression. These studies suggest that the presence of immune complexes in infection or autoimmunity may radically alter the nature of CD163-depen- dent monocyte/macrophage processes. This may be particularly important in disease states in which immune complexes and high levels of free Hb are present, such as in autoimmune hemolytic anemia, transfusion reactions, or infections by hemolytic bacteria. J. Leukoc. Biol. 76: 000-000; 2004.