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Cross‐linking of FcγR triggers shedding of the hemoglobin‐haptoglobin scavenger receptor CD163
Author(s) -
Sulahian Timothy H.,
Pioli Patricia A.,
Wardwell Kathleen,
Guyre Paul M.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1003523
Subject(s) - cd163 , biology , haptoglobin , scavenger receptor , tumor necrosis factor alpha , immunology , lipopolysaccharide , monocyte , macrophage , immune system , biochemistry , lipoprotein , cholesterol , in vitro
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 α (TNF‐α), surface CD163 is proteolytically cleaved from the plasma membrane in response to lipopolysaccharide (LPS) stimulation. As cross‐linking of the Fcγ receptor (FcγR) is similarly known to induce TNF‐α shedding, the effect of FcγR stimulation on CD163 shedding was investigated. We found that FcγR 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 FcγR stimulation in short‐term cultures suppressed CD163 mRNA expression, long‐term cultures of monocytes treated with LPS—but not with a FcγR 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.