Characterization and isolation of a C-reactive protein receptor from the human monocytic cell line U-937.
Human C-reactive protein (CRP) is an acute phase reactant that is opsonic and an activator of macrophage tumoricidal function. CRP also activates the classical C cascade. These activities suggest that CRP might interact with monocytes/macrophages via specific receptors in a manner analogous to the interaction of IgG with FcR. With the use of radio-labeled human CRP, we have observed specific binding of CRP to human blood monocytes and the human monocytic cell line U-937. Binding was saturable at a pathophysiologic concentration of CRP, with an estimated KD of 9.5 x 10(-8) M and 3.6 x 10(5) binding sites/cell. Specific binding was inhibited by polyclonal human IgG as well as an IgG1 myeloma. In the converse experiment, CRP failed to inhibit specific [125I]IgG binding. The mAb IV.3, which inhibits binding of IgG immune complexes to FcRII, did not inhibit CRP binding. A 100-fold excess of phosphorylcholine or the phosphorylcholine binding peptide of CRP (residues 47-63) failed to inhibit binding. Although human rIFN-gamma and PMA increased FcRI expression, these reagents had no affect on CRP receptor expression. A single membrane protein of 38 to 41 kDa from U-937 cells was chemically cross-linked to [125I]CRP; the cross-linking was inhibited by human IgG1 but not the IV.3 mAb. Furthermore, two membrane proteins with a Mr of 38 to 40 kDa and 58 to 60 kDa were isolated by CRP ligand-affinity chromatography. These proteins were of a distinct size from those isolated for FcRI from an IgG ligand matrix. These studies demonstrate specific binding of human CRP to a human monocytic cell line via receptors that are distinct from the IgG FcR and implicate CRP in nonspecific, preimmune host defense reaction mediated by cells of the monocytic lineage.
Tebo
J M
JM
Department of Microbiology, Ohio State University, Columbus 43210-1292.
Mortensen
R F
RF
D002097:C-Reactive Protein / Q000378:metabolism*; D002460:Cell Line; D003432:Cross-Linking Reagents; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D008970:Molecular Weight; D009000:Monocytes / Q000032:analysis*; D010767:Phosphorylcholine / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000302:isolation & purification* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003432:Cross-Linking Reagents; D007074:Immunoglobulin G; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D010767:Phosphorylcholine; D007371:Interferon-gamma; D002097:C-Reactive Protein; D013755:Tetradecanoylphorbol Acetate