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(Journal of Leukocyte Biology. 2002;72:711-717.)
© 2002 by Society for Leukocyte Biology

Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163

Katharine A. Hintz^*, Athos J. Rassias, Kathleen Wardwell^*, Marcia L. Moss, Peter M. Morganelli^,||, Patricia A. Pioli^*, Alice L. Givan^*, Paul K. Wallace, Mark P. Yeager and Paul M. Guyre^*

Departments of
^* Physiology and
Microbiology, Dartmouth Medical School, Hanover, New Hampshire;
Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire;
Cognosci, Inc., Research Triangle Park, North Carolina; and
^|| Department of Microbiology, Veterans Administration Hospital, White River Junction, Vermont

Correspondence: Dr. Paul M. Guyre, Department of Physiology, Dartmouth Medical School, 1 Medical Center Dr., 740 W. Borwell Bldg., Lebanon, NH 03756-0001. E-mail: Paul.M.Guyre{at}dartmouth.edu

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.

Key Words: lipopolysaccharide • glucocorticoid • inflammation • in vivo • sepsis

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