Hintz Katharine A, Rassias Athos J, Wardwell Kathleen, Moss Marcia L, Morganelli Peter M, Pioli Patricia A, Givan Alice L, Wallace Paul K, Yeager Mark P, Guyre Paul M
Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire, USA.
J Leukoc Biol. 2002 Oct;72(4):711-7.
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.
CD163是一种单核细胞和巨噬细胞特异性表面糖蛋白，可被白细胞介素-10和糖皮质激素上调，是血红蛋白/触珠蛋白复合物的清道夫受体。我们报告了静脉注射脂多糖（LPS）的人类志愿者血浆中可溶性CD163迅速且高度可重复的升高。我们还表明，LPS诱导分离的单核细胞表面的CD163脱落，确定单核细胞和巨噬细胞的脱落是体内内毒素血症相关血浆CD163升高的可能机制。使用抑制剂TAPI-0的研究表明，金属蛋白酶负责LPS介导的CD163脱落。最后，我们证明实验性内毒素血症后24小时循环单核细胞表面CD163表达显著增加。这些发现表明，CD163可响应细菌内毒素而迅速动员。由于血红蛋白可结合LPS并增强其毒性，确定细胞表面和可溶性CD163如何影响脓毒症期间的炎症过程将很重要。
