Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163.
CD163, a monocyte and macrophage-specific surface glycoprotein, which is increased by interleukin-10 and glucocorticoids, is a scavenger receptor for hemoglobin/haptoglobin complexes. We report a rapid and highly reproducible rise in soluble CD163 in the plasma of human volunteers given intravenous lipopolysaccharide (LPS). We also show that LPS induces shedding of CD163 from the surface of isolated monocytes, identifying shedding from monocytes and macrophages as a likely mechanism for the endotoxemia-associated rise in plasma CD163 in vivo. Studies using the inhibitor TAPI-0 indicate that a metalloproteinase is responsible for LPS-mediated shedding of CD163. Finally, we demonstrate a marked increase in surface CD163 expression on circulating monocytes 24 h following experimental endotoxemia. These findings show that CD163 is rapidly mobilized in response to bacterial endotoxin. As hemoglobin can bind LPS and enhance its toxicity, it will be important to determine how cell surface and soluble CD163 influence inflammatory processes during sepsis.
Hintz
Katharine A
KA
Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire, USA.
Rassias
Athos J
AJ
Wardwell
Kathleen
K
Moss
Marcia L
ML
Morganelli
Peter M
PM
Pioli
Patricia A
PA
Givan
Alice L
AL
Wallace
Paul K
PK
Yeager
Mark P
MP
Guyre
Paul M
PM
D002462:Cell Membrane / Q000276:immunology; D004151:Dipeptides / Q000494:pharmacology; D019446:Endotoxemia / Q000097:blood* / Q000276:immunology; D006877:Hydroxamic Acids / Q000494:pharmacology; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000097:blood*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011971:Receptors, Immunologic / Q000097:blood*; D051116:Receptors, Scavenger; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation
C417665:CD163L1 protein, human; D004151:Dipeptides; D006877:Hydroxamic Acids; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C092152:N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D008666:Metalloendopeptidases; D013755:Tetradecanoylphorbol Acetate