Munford R S, Andersen J M, Dietschy J M
J Clin Invest. 1981 Dec;68(6):1503-13. doi: 10.1172/jci110404.
When gram-negative bacterial lipopolysaccharides (LPS) are injected intravenously into the rabbit or rat, they bind to plasma lipoproteins, particularly high density lipoproteins (HDL). The present studies were performed to examine the mechanisms by which LPS-HDL complexes are removed from the circulation and taken up by various tissues. Our approach was to compare the sites of specific tissue binding and uptake of HDL and of LPS-HDL complexes in the rat and squirrel monkey. In the rat, binding of homologous 125I-HDL was demonstrated principally in the adrenal gland, ovary, liver, and spleen. [3H]LPS-HDL complexes (produced in vitro by incubating Salmonella typhimurium [3H]LPS with rat HDL and lipoprotein-free plasma) bound to the same tissues, but with apparently lower affinities. The specificity of binding of both 125I-HDL and [3H]LPS-HDL to these organs was demonstrated in two ways. First, tissue binding of both radiolabeled preparations was swamped out by raising the circulating levels of HDL-cholesterol from 32 to 140 mg/dl. Second, treatment of the animals with dexamethasone abolished specific binding of both HDL preparations to the adrenal gland while administration of adrenocorticotropin increased the specific adrenal binding of the two preparations. The steady-state plasma clearance rate for 125I-HDL equaled 774 +/- 29 microliters/h and was significantly lower (557 +/- 39 microliters/h) for the LPS-HDL complex, a finding that presumably reflected the lesser ability of the various tissues to bind the LPS-HDL complex. Binding studies were also done in the squirrel monkey, an animal that has the same level of circulating HDL cholesterol as the rat, but nearly three times more cholesterol in low density lipoproteins. Specific binding of homologous 125I-HDL and [3H]LPS-HDL was again found principally in the adrenal gland and liver. The results indicate that the sites of tissue uptake of bacterial LPS are strongly influenced by binding of LPS to HDL. In particular, LPS-HDL binding may be an important determinant of the extent to which LPS are taken up by the adrenal gland during bacterial sepsis.
当将革兰氏阴性菌脂多糖（LPS）静脉注射到兔或大鼠体内时，它们会与血浆脂蛋白结合，尤其是高密度脂蛋白（HDL）。进行本研究以检查LPS - HDL复合物从循环中清除并被各种组织摄取的机制。我们的方法是比较大鼠和松鼠猴中HDL以及LPS - HDL复合物在特定组织中的结合和摄取部位。在大鼠中，同源125I - HDL的结合主要在肾上腺、卵巢、肝脏和脾脏中得到证实。[3H]LPS - HDL复合物（通过将鼠伤寒沙门氏菌[3H]LPS与大鼠HDL和无脂蛋白血浆在体外孵育产生）与相同组织结合，但亲和力明显较低。125I - HDL和[3H]LPS - HDL与这些器官结合的特异性通过两种方式得到证实。首先，将HDL - 胆固醇的循环水平从32mg/dl提高到140mg/dl会使两种放射性标记制剂的组织结合被淹没。其次，用地塞米松治疗动物会消除两种HDL制剂与肾上腺的特异性结合，而给予促肾上腺皮质激素会增加两种制剂与肾上腺的特异性结合。125I - HDL的稳态血浆清除率为774±29微升/小时，而LPS - HDL复合物的清除率明显较低（557±39微升/小时），这一发现可能反映了各种组织结合LPS - HDL复合物的能力较弱。还在松鼠猴中进行了结合研究，松鼠猴的循环HDL胆固醇水平与大鼠相同，但低密度脂蛋白中的胆固醇几乎是大鼠的三倍。再次发现同源125I - HDL和[3H]LPS - HDL的特异性结合主要在肾上腺和肝脏中。结果表明，细菌LPS的组织摄取部位受到LPS与HDL结合的强烈影响。特别是，LPS - HDL结合可能是细菌败血症期间肾上腺摄取LPS程度的重要决定因素。
