Cross-linking of FcgammaR triggers shedding of the hemoglobin-haptoglobin scavenger receptor CD163.
CD163, the hemoglobin (Hb)-haptoglobin scavenger receptor, is a monocyte/macrophage-restricted member of the scavenger receptor, 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 necrosis factor alpha (TNF-alpha), surface CD163 is proteolytically cleaved from the plasma membrane in response to lipopolysaccharide (LPS) stimulation. As cross-linking of the Fcgamma receptor (FcgammaR) is similarly known to induce TNF-alpha shedding, the effect of FcgammaR stimulation on CD163 shedding was investigated. We found that FcgammaR stimulation resulted in a rapid release of surface CD163 into the supernatant that was blocked by inhibitors of protein kinase C and tyrosine kinases. Although LPS and FcgammaR stimulation in short-term cultures suppressed CD163 mRNA expression, long-term cultures of monocytes treated with LPS-but not with a FcgammaR cross-linking reagent-resulted in an interleukin-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-dependent 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.
Sulahian
Timothy H
TH
Department of Physiology, Dartmouth Medical School, Lebanon, NH, USA. tsulahia@hsph.harvard.edu
Pioli
Patricia A
PA
Wardwell
Kathleen
K
Guyre
Paul M
PM
D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000187:drug effects / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017452:Receptors, IgG / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D016753:Interleukin-10; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C