THE CELL-WALL COMPONENTS PEPTIDOGLYCAN AND LIPOTEICHOIC ACID FROM STAPHYLOCOCCUS-AUREUS ACT IN SYNERGY TO CAUSE SHOCK AND MULTIPLE ORGAN FAILURE
THE CELL-WALL COMPONENTS PEPTIDOGLYCAN AND LIPOTEICHOIC ACID FROM STAPHYLOCOCCUS-AUREUS ACT IN SYNERGY TO CAUSE SHOCK AND MULTIPLE ORGAN FAILURE
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DOI：
10.1073/pnas.92.22.10359
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发表时间：
1995-10-24
影响因子：
11.1
通讯作者：
VANE, JR
中科院分区：
文献类型：
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作者：
DEKIMPE, SJ;KENGATHARAN, M;VANE, JR
虽然革兰氏阳性脓毒症的发病率已大幅上升，但目前尚不清楚革兰氏阳性微生物（无内毒素）如何引发脓毒性休克。我们研究了金黄色葡萄球菌的两种细胞壁成分肽聚糖（PepG）和脂磷壁酸（LTA）是否可以诱导革兰氏阳性菌引起的感染性休克相关的炎症反应和多器官功能障碍综合征（MODS）。在培养的巨噬细胞中，LTA（10 μ g/ml），而不是PepG（100 μ g/ml），诱导一氧化氮的释放，测量为亚硝酸盐。然而，PepG引起LTA引起的亚硝酸盐产生增加4倍。此外，PepG抗体抑制由杀死的S引起的亚硝酸盐释放。金黄色。施用PepG（10 mg/kg; i. v.）和LTA（3mg/kg; i.v.）导致肿瘤坏死因子α和干扰素γ的释放和MODS，如动脉氧压（肺）的降低和胆红素和丙氨酸氨基转移酶（肝）、肌酸酐和尿素（肾）、脂肪酶（胰腺）和肌酸激酶（心脏或骨骼肌）的血浆浓度的增加所示。在这些器官中也有诱导型一氧化氮合酶的表达，循环衰竭和50%的死亡率。在单独施用PepG或LTA后未观察到这些作用。即使是高剂量的LTA（10 mg/kg）也只会导致循环衰竭，但不会导致MODS。因此，我们的研究结果表明，两种细菌壁组分PepG和LTA共同作用，导致与革兰氏阳性微生物相关的全身性炎症和多系统衰竭。
Although the incidence of Gram-positive sepsis has risen strongly, it is unclear how Gram-positive organisms (without endotoxin) initiate septic shock. We investigated whether two cell wall components from Staphylococcus aureus, peptidoglycan (PepG) and lipoteichoic acid (LTA), can induce the inflammatory response and multiple organ dysfunction syndrome (MODS) associated with septic shock caused by Gram-positive organisms. In cultured macrophages, LTA (10 mu g/ml), but not PepG (100 mu g/ml), induces the release of nitric oxide measured as nitrite. PepG, however, caused a 4-fold increase in the production of nitrite elicited by LTA. Furthermore, PepG antibodies inhibited the release of nitrite elicited by killed S. aureus. Administration of both PepG (10 mg/kg; i.v.) and LTA (3 mg/kg; i.v.) in anesthetized rats resulted in the release of tumor necrosis factor a: and interferon gamma and MODS, as indicated by a decrease in arterial oxygen pressure (lung) and an increase in plasma concentrations of bilirubin and alanine aminotransferase (liver), creatinine and urea (kidney), lipase (pancreas), and creatine kinase (heart or skeletal muscle). There was also the expression of inducible nitric oxide synthase in these organs, circulatory failure, and 50% mortality. These effects were not observed after administration of PepG or LTA alone. Even a high dose of LTA (10 mg/kg) causes only circulatory failure but no MODS. Thus, our results demonstrate that the two bacterial wall components, PepG and LTA, work together to cause systemic inflammation and multiple systems failure associated with Gram-positive organisms.