RECOGNITION AND PLASMA-CLEARANCE OF ENDOTOXIN BY SCAVENGER RECEPTORS
RECOGNITION AND PLASMA-CLEARANCE OF ENDOTOXIN BY SCAVENGER RECEPTORS
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DOI：
10.1038/352342a0
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发表时间：
1991-07-25
期刊：
影响因子：
64.8
通讯作者：
RAETZ, CRH
中科院分区：
文献类型：
--
作者：
HAMPTON, RY;GOLENBOCK, DT;RAETZ, CRH
脂质A是脂多糖（LPS，也称为内毒素）的活性部分，是革兰氏阴性菌的表面组分，可刺激巨噬细胞活化并引起内毒素休克1，2。 巨噬细胞能结合、内化和部分降解LPS、脂质A及其生物活性前体脂质IV（A）（参考文献3-7）。我们在这里报告说，巨噬细胞样RAW 264.7细胞与脂质IV（A）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。清道夫受体配体抑制脂质IV（A）与RAW细胞的结合和RAW细胞的代谢，并且脂质IV（A）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RAW细胞的体外竞争研究表明，清道夫受体结合不参与LPS或脂质IV（A）诱导的巨噬细胞刺激，但体内研究表明，清道夫受体配体极大地抑制了小鼠肝脏对脂质IV（A）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起重要作用。
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 1,2. Macrophages can bind, internalize and partially degrade LPS, lipid A and its bioactive precursor, lipid IV(A) (refs 3-7). We report here that lipid IV(A) 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 IV(A) binding to, and metabolism by, RAW cells, and lipid IV(A) 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 IV(A)-induced stimulation of macrophages, in vivo studies show that scavenger-receptor ligands greatly inhibit hepatic uptake of lipid IV(A) in mice. Thus, scavenger receptors expressed on macrophages may have an important role in the clearance and detoxification of endotoxin in animals.