Hampton R Y, Golenbock D T, Penman M, Krieger M, Raetz C R
Department of Biochemistry, University of Wisconsin-Madison 53706.
Nature. 1991 Jul 25;352(6333):342-4. doi: 10.1038/352342a0.
Lipid A is the active moiety of lipopolysaccharide (LPS, also referred to as endotoxin), a surface component of Gram-negative bacteria that stimulates macrophage activation and causes endotoxic shock. Macrophages can bind, internalize and partially degrade LPS, lipid A and its bioactive precursor, lipid IVA. We report here that lipid IVA binding and subsequent metabolism to a less active form by macrophage-like RAW 264.7 cells is mediated by the macrophage scavenger receptor. Scavenger-receptor ligands inhibit lipid IVA binding to, and metabolism by, RAW cells, and lipid IVA binds to type I and type II bovine scavenger receptors on transfected Chinese hamster ovary cells. Although in vitro competition studies with RAW cells indicate that scavenger receptor binding is not involved in LPS or lipid IVA-induced stimulation of macrophages, in vivo studies show that scavenger-receptor ligands greatly inhibit hepatic uptake of lipid IVA in mice. Thus, scavenger receptors expressed on macrophages may have an important role in the clearance and detoxification of endotoxin in animals.
脂多糖（LPS，也称为内毒素）的活性部分是脂质A，它是革兰氏阴性菌的一种表面成分，可刺激巨噬细胞活化并导致内毒素休克。巨噬细胞能够结合、内化并部分降解LPS、脂质A及其生物活性前体脂质IVA。我们在此报告，巨噬细胞样RAW 264.7细胞对脂质IVA的结合以及随后代谢为活性较低的形式是由巨噬细胞清道夫受体介导的。清道夫受体配体可抑制脂质IVA与RAW细胞的结合及其代谢，并且脂质IVA可与转染的中国仓鼠卵巢细胞上的I型和II型牛清道夫受体结合。尽管对RAW细胞的体外竞争研究表明，清道夫受体结合并不参与LPS或脂质IVA诱导的巨噬细胞刺激，但体内研究表明，清道夫受体配体可极大地抑制小鼠肝脏对脂质IVA的摄取。因此，巨噬细胞上表达的清道夫受体可能在动物体内内毒素的清除和解毒中发挥重要作用。
