AST/ALT比值在慢性肝病患者中的特点和判断预后价值

目的 分析不同病因、不同病情的慢性肝病患者天冬氨酸氨基转移酶和丙氨酸氨基转移酶比值(AST/ALT)的特点,评价AST/ALT比值判断慢性肝病患者预后方面的价值.方法 对534例不同病因的肝硬化、原发性肝癌患者的住院资料进行分析,比较各类患者AST/ALT比值的特点.运用接受者运行曲线(ROC)及曲线下面积,比较AST/ALT比值与终末期肝病模型(MELD)、Child-Turcotte-Pugh(CTP)分级(CC)和评分(CS)在判断慢性肝病患者中短期预后方面的准确性;运用非参数相关分析,计算Spearman相关系数,分析三者之间的相关性.结果 在原发性肝癌患者,AST/ALT比值明显高于肝硬化患者(P＜0.05);病毒性肝病患者和非病毒性肝病患者的AST/ALT比值无明显差异(P=0.852).死亡患者的AST/ALT比值明显高于生存患者的平均值(P=0.000);随着CTP分级的升高,AST/ALT比值也逐渐升高,A、B、C三级之间的AST/ALT比值具有显著差异(P＜0.05).AST/ALT比值和MELD、CS及CC在判断慢性肝病患者生存3个月的ROC曲线下面积分别是0.88、0.92、0.69和0.59,判断生存1年时间的ROC曲线下面积分别为0.64、0.77、0.65和0.63;AST/ALT比值与MELD、CS和CC三者之间的相关系数分别是0.185、0.291和0.297(P=0.000).结论 AST/ALT比值随着肝脏病变的加重而逐渐升高.AST/ALT比值和MELD在判断慢性肝病患者短期预后方面是较好的指标.AST/ALT比值和MELD、CS、CC三者之间具有显著相关性.     

葛花醒酒养胃颗粒对酒精性肝病内毒素损伤的防治作用

目的探讨葛花醒酒养胃颗粒对酒精性肝病(ALD)内毒素损伤的防治作用.方法Wistar大鼠48只随机分为正常组、模型组、葛花醒酒养胃颗粒治疗组(简称治疗组)和肝泰乐对照组(简称对照组).实验采用梯度酒精定量灌胃法制备酒精性肝病大鼠模型,造模同时治疗组予葛花醒酒养胃颗粒汤150mg·kg-1·d-1,分2次灌胃,对照组予肝泰乐水38mg·kg-1·d-1,分2次灌胃,正常组予同容积生理盐水,每日灌胃2次,连续灌胃8周后采血,检测大鼠血浆内毒素(LPS)、血清酶(ALT、AST、GGT)、血脂(Tch、TG)及血清肿瘤坏死因子(TNF-α)的含量,同时用RT-PCR法测定肝组织中脂多糖结合蛋白(LBP)和脂多糖受体CD14mRNA的表达.结果模型组大鼠血浆内毒素和血清TNF-α水平明显高于对照组(P＜0.05),肝组织中LBP和CD14mRNA的表达明显高于对照组(P＜0.05);同时血清ALT、AST、GGT、TG明显升高(P＜0.05);治疗组血浆内毒素和血清TNF-α水平明显低于模型组(P＜0.05),LBP和CD14mRNA的表达明显低于对照组(P＜0.05),血清ALT、AST、GGT、TG水平明显降低(P＜0.05).结论葛花醒酒养胃颗粒对大鼠酒精性肝损伤有较好的防治作用.     

酒精性与非酒精性脂肪性肝病血脂代谢异常特点

目的研究脂肪性肝病患者的血脂变化及其二者的相互关系。方法收集我院2007年~2012年肝病门诊及病房收治的139例脂肪性肝病患者,分为酒精性脂肪性肝病组(A组),非酒精性肝病组(B组)。其中将两组又各自分为肝炎组和肝硬化组,分别对两组的血脂与肝功能、血糖、血常规、体重指数、年龄、饮酒史、肝胆彩超、心电图等指标进行对比分析。结果酒精性肝病组(A组)肝功能AST、GGT、TBIL显著升高,ALB、HDL、LDL显著降低,其中酒精性肝硬化患者的ALT、AST、GGT、ALB、TG、TC、HDL等相关生化指标较肝炎组明显降低,TBIL显著升高。非酒精性脂肪性肝病(B组)肝功能ALT显著升高,血脂(HDL、LDL)显著升高,其肝硬化患者的ALB、TG水平较肝炎组显著降低,TBIL升高,其他生化指标ALT、AST、GGT、TC、HDL降低不显著。两组肝功能的ALB与血脂(TG、TC、HDL、LDL)有相关性,差异有统计学意义(P0.05);肝功能中ALT、AST、GGT、TBIL与血脂在两组中的差异不明显。结论脂肪性肝病患者存在血脂变化,酒精性肝病以高密度脂蛋白胆固醇为主,非酒精性肝病以高密度脂蛋白胆固醇和低密度脂蛋白胆固醇均明显异常。脂肪性肝病患者肝功能白蛋白与血脂密切相关。     

应用ROC曲线评价酒精性肝病实验室诊断指标的价值

目的探讨缺糖转铁蛋白(CDT)和GGT、ALT、AST对酒精性肝病(ALD)的诊断价值。方法选取38例ALD患者,40例非酒精性肝病(NALD),40例嗜酒者和40例健康人用离子交换色谱与免疫比浊法结合检测CDT,使用TBA-120FR全自动生化分析仪检测GGT、AST、ALT,用ROC曲线进行分析。结果CDT诊断ALD的ROC曲线下面积(AUC)为0.894,敏感性为0.821,特异性为0.797,而GGT这三者分别为0.804、0.800、0.633,ALT分别为0.533、0.314、0.541,AST分别为0.525、0.343、0.574。结论CDT、GGT对ALD的实验室诊断具有一定的价值,其中CDT优于GGT是最好的辅助诊断指标。     

ANI指数可鉴别脂肪肝病因

鉴别酒精性脂肪肝抑或非酒精性脂肪肝基于临床和脂肪肝组织学检查往往较困难，主要是由于不可靠的饮酒史，而用于鉴别酒精性脂肪肝抑或非酒精性脂肪肝的各种生物学标志物也较为有限，美国梅奥医院Dunn医师等进行的一项横断面队列研究显示，根据平均红细胞容积（MCV）、天门冬酸氨基转移酶（AST）／丙氨酸氨基转移酶（ALT）比值、体质指数（BMI）和性别建立一种新的模型，得出的ANI指数能够鉴别酒精性肝病（ALD）和非酒精性脂肪肝病（NAFLD）。     

酒精性与非酒精性脂肪肝的临床特征鉴别探讨

目的探讨酒精性与非酒精性脂肪肝的临床特征及其鉴别诊断方法。方法随机选择非酒精性、酒精性脂肪肝各20例患者进行临床对比研究。结果酒精性脂肪肝患者血浆白蛋白(A)含量、A／G(血浆白球蛋白比值)降低，血清γ-谷氨酰转移酶(CGT)、血清门冬氨酸氨基转移酶(AST)／丙氨酸氨基转移酶(ALT)比值升高。结论酒精性脂肪肝患者上述临床特征对与非酒精性脂肪肝鉴别诊断有一定意义。     

饮酒与肝功能及红细胞参数的关系

目的:探讨饮酒与肝功能及红细胞参数的相关性. 方法:选择我院2007-2009年住院的酒精性肝病(alcoholic liver disease,ALD)患者312例,与年龄相仿的正常非饮酒者40例作对照,进行肝功能和红细胞参数的测定,并与饮酒量和饮酒时间进行比较. 结果:酒精性肝病患者丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、谷氨酰基转换酶(GGT)、甘氨胆酸(CG)和平均红细胞体积(MCV)、平均血红蛋白量(MCH)均显著高于对照组(P<0.001),而红细胞比容(HCT)显著下降(P<0.001),其变化与饮酒时间和饮酒量密切相关(r=0.61,0.59,均P<0.01). 结论:长期饮酒可导致肝酶和红细胞参数异常,动态监测饮酒者GGT、ALT和AST有助于酒精性肝病的诊断,MCV可作为危险饮酒的监测指标.     

《肝脏》杂志常用医学名词缩写

<正>AFP甲胎蛋白alpha-fetoprotein AIDS艾滋病aquired immune deficiency syndrome AIH自身免疫性肝炎autoimmune hepatitis Alb白蛋白albumin ALD酒精性肝病alcoholic liver disease ALF急性肝功能衰竭acute liver failure ALP碱性磷酸酶alkaline phosphatase ALT丙氨酸氨基转移酶alanine aminotransferase AST天冬氨酸氨基转移酶aspartic aminotransferase     

血清精氨酸代琥珀酸裂解酶的测定在肝病诊断中的意义

目的探讨血清精氨酸代琥珀酸裂解酶（ASL）对肝病的诊断效能。方法测定291例肝病患者、247例非肝病患者和32名健康对照血清ASL和ALT、AST、GGT、LDH、ALP活性及TBil浓度；其中31例肝病患者进行了病理组织学检查。结果ROC曲线显示ASL对判断肝病的敏感度为100．0％，特异性为91．1％（分界值=8．0U／L）；ALT和AST的敏感度为97．60%和83．8％，特异性仅分别为24．7％和28．3％（分界值=40．0U／L）。ASL在不同肝病的变化情况是肝癌〉急性肝炎〉肝硬化〉慢性肝炎；ASL浓度[（86．9±26．5）u／L]与肝病理组织学炎症活动度计分（9．83±3．36）呈正相关（r=0．417，P=0．019）。结论ASL诊断肝病的敏感度、特异性优于AST和ALT，是肝病诊断的有用指标。     

60例肝移植患者血清ALT、AST及LDH变化分析

目的研究肝移植患者术前及术后血清丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）和乳酸脱氢酶（LDH）的变化规律,探讨其临床价值。方法采用全自动生化分析仪Olympus AU5400检测60例成功进行肝移植手术患者的血清ALT、AST及LDH等3项生化指标,观察这些指标在术前1d、术后1、10、20、30d及术后1年的动态变化和相互关系。结果ALT、AST及LDH在术后1d均明显升高（P〈0．01）,并于术后10d明显下降（P〈0．01）,3项指标间在肝移植术前及术后均具有良好的相关性;术后ALT变化出现“双峰”波动的患者,第二次ALT升高多出现在20～30d,且升高幅度较低。结论ALT、AST和LDH是肝移植术后早期反映肝功能状况的可靠指标,其不同时期的变化波动及相互关系为肝移植的效果评价及预后提供了重要依据。     

The -159C/T polymorphism in the promoter region of the CD14 gene is associated with advanced liver disease and higher serum levels of acute-phase proteins in heavy drinkers

BACKGROUND: Innate inflammatory responses to endotoxin (lipopolysaccharide) contribute to the development of alcoholic liver disease (ALD). A single-nucleotide polymorphism (-159C/T) in the promoter region of the gene coding for CD14 (a lipopolysaccharide receptor) could be associated with the development of ALD. We sought too investigate the relationship between the CD14/-159C/T polymorphism and advanced ALD and acute-phase protein levels in heavy drinkers. METHODS: A total of 138 heavy drinkers consecutively admitted to an Internal Medicine department were genotyped for the CD14/-159C/T polymorphism. Serum samples were analyzed for lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), C-reactive protein (CRP), and immunoglobulin (Ig) A, IgG, and IgM. Patients with ascites or liver encephalopathy (n = 35) were classified as having advanced ALD. RESULTS: After adjusting for potential confounding variables, the CD14/-159TT genotype was positively associated with advanced ALD (odds ratio, 2.99; 95% confidence interval, 1.09-8.24, p = 0.03) and serum LBP (p = 0.01) and sCD14 (p = 0.04) levels. The CD14/-159C/T polymorphism was not associated with serum levels of CRP, IgA, IgG, or IgM. CONCLUSIONS: Our results support the notion that CD14/-159TT homozygous heavy drinkers have higher levels of the LPS-binding acute-phase proteins (LBP and sCD14) than do carriers of the CD14/-159C allele. Also, the CD14/-159TT genotype may be a risk factor for advanced ALD.     

Endotoxin and its binding proteins in chronic liver disease: the effect of transjugular intrahepatic portosystemic shunting

BACKGROUND: Gut-derived endotoxin is insufficiently cleared by the diseased liver, and thus, is elevated in plasma of patients with chronic liver disease (CLD). Endotoxin action might be modified by binding to soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), both of which have not yet been sufficiently studied in CLD. METHODS: Endotoxin, sCD14 and LBP have been determined in peripheral blood of 72 patients and 39 control subjects, and in portal and hepatic venous blood of 12 patients during transjugular intrahepatic portosystemic shunt (TIPS) implantation. RESULTS: Peripheral endotoxin (average 3-fold increased compared to controls), LBP, and sCD14 plasma levels were elevated in chronic liver disease irrespective of Child stage m, preserve/absence of cirrhosis or aetiology. LBP, and sCD14. Furthermore, endotoxin levels in the portal vein (38.1 +/- 6.1 pg/ml) were only slightly elevated compared to the hepatic vein (29.2 +/- 4.4 pg/ml), and peripheral endotoxin levels did not increase after TIPS. CONCLUSIONS: Decreased hepatocellular function rather than hepatic blood shunting might be responsible for endotoxemia. The elevation in LBP and sCD14 levels may be a consequence of endotoxemia.     

Endotoxin, endotoxin-neutralizing-capacity, sCD14, sICAM-1, and cytokines in patients with various degrees of alcoholic liver disease

BACKGROUND: Chronic alcohol ingestion leads to endotoxemia which is believed to play an important role in the pathogenesis of alcoholic liver disease (ALD). The purpose of this study was to determine if chronic ethanol consumption, in addition to affecting plasma endotoxin and cytokines, also affects the endotoxin-neutralizing capacity (ENC), sCD14, and sICAM-1, in patients with ALD. A second aim was to identify correlations between these latter parameters, endotoxin, and cytokines, especially IL-10. METHODS: Hospitalized patients with various degrees of ALD (n = 59), and 20 healthy volunteers were studied. Plasma endotoxin and ENC were determined using our kinetic Limulus amebocyte lysate test. Cytokines, sCD14, and sICAM-1 were measured by enzyme-linked immunosorbent assay. RESULTS: Patients with ALD exhibited a mild endotoxemia (p < 0.01) and a marked decrease in ENC (p < 0.0002). TNF-alpha (p < 0.05), IL-6 (p < 0.0001), sICAM (p < 0.005), and sCD14 (p < 0.0005) were significantly elevated in all patients with ALD, and IL-10 (p < 0.05) in patients with cirrhotic ALD. With the exception of IL-10, the cytokines correlated with each other and with sICAM-1. No correlations occurred between endotoxin, ENC, and sCD14, and between these and the cytokines and sICAM-1. Elevated levels of endotoxin correlate with acute excessive alcohol ingestion. No gender differences were observed. CONCLUSIONS: Acute alcohol intoxication rather than severe ALD results in significant endotoxemia. The limited capacity of plasma to neutralize endotoxin in liver injury seems to be an important factor in ALD which may be responsible for the release of endotoxin-induced mediators, such as cytokines, as well as s-ICAM-1, that are relevant in the pathogenesis of ALD.     

sCD14 prevents endotoxin inducible oxidative burst response of human monocytes.

Luminol-enhanced chemiluminescence (LECL) was used to determine the effect of soluble CD14 (sCD14) on the endotoxin inducible generation of reactive oxygen species in human monocytes. LPS is unable to activate monocytes under serum free conditions, but LECL responses were measured after pretreatment of LPS stock solution with serum, according to Wright et al., who described a LPS-binding protein (LBP), necessary for mediating LPS binding to the receptor CD14 on monocyte surfaces. In normal human serum a soluble form of CD14 (sCD14) exists, from which nothing is known about its possible function. sCD14 reduces the endotoxin inducible monocyte activation in our in vitro model in a dose dependent manner (5-30 micrograms/ml) suggesting an immunomodulatory function. Therefore it seems to be a new candidate for a therapeutic concept in endotoxic shock prevention.     

脂多糖/脂多糖结合蛋白复合物的初步构建

目的采用温孵法构建脂多糖/脂多糖结合蛋白(LPS/LBP)复合物,研究LPS炎症信号通路。方法将LPS与LBP按15︰1、10︰1、5︰1的比例混匀。把LPS/LBP混合物、LBP(浓度分别为200μg/ml、100μg/ml和50μg/ml)、LPS(浓度分别为100μg/ml、50μg/ml)过夜孵育。将孵育后的LPS/LBP混合物、LBP、LPS行凝胶电泳,经考马斯亮蓝染色后将各染色条带切取,行蛋白回收,并测定内毒素。结果凝胶电泳后,LPS/LBP复合物、LBP泳道于相对分子质量52×10~3处可见考马斯亮兰染色的条带。样本中LBP浓度越高、条带染色越浓,LPS泳道对应于相对分子质量52×10~3处无染色条带出现。各浓度比例的LPS/LBP复合物电泳后凝胶条带回收物中均能检测出内毒素。10︰1 LPS/LBP复合物组、15︰1 LPS/LBP复合物组复合物内毒素浓度显著高于5︰1 LPS/LBP复合物组内毒素浓度(P0.05)。10︰1 LPS/LBP复合物组与15︰1 LPS/LBP复合物组内毒素浓度无统计学差异(P0.1)。各浓度LBP组均未检出内毒素,各LPS组内毒素检测也为阴性。结论 LPS︰LBP为10︰1是较为合理的构建LPS/LBP复合物的比例,通过温孵及凝胶电泳可获得纯度较高的LPS/LBP复合物。     

实验性酒精性肝病时脂多糖结合蛋白和脂多糖受体CD14的表达

目的观察大鼠酒精性肝病时脂多糖结合蛋白(lipopolysaccharide binding protein,LBP)和脂多糖受体CD14的表达及其在酒精性肝损害中的作用.方法随机将Wistar大鼠分为乙醇喂养组和葡萄糖喂养对照组,分剐在饮水中加入乙醇(剂量5-12 g@kg-1@d-1)和相同量的葡萄糖.两组大鼠分别于4周和8周测定其血浆中内毒揪素(LPS)浓度及血清中ALT变化,同时用RT-PCR测定肝组织中LBP和CD14 mRNA的表达,并在光镜和电镜下观察肝脏的形态学改变.结果乙醇喂养组4周和8周时大鼠血浆LPS浓度分别为(129±21)pg/ml和(187±35)Pg/m1,明显高于对照组的(48±9)pg/ml和(53±11)pg/ml(f值分别为11.2和11.6,P＜0.05);乙醇组大鼠血清ALT浓度为(112±15)U/L和(147±22)U/L,也明显高于对照组的(31±12)U/L和(33±9)U/L(t值分别为5.9和20.6,P＜0.05).乙醇组大鼠肝组织中LBP和CD14 mRNA的表达水平明显高于对照组(P＜0.05),其肝组织发生显著的病理变化,主要表现为脂肪变性、炎性细胞浸润及细胞坏死.对照组肝组织中LBP和CD14mRNA无明显表达,其病理变化也不明显.结论乙醇能诱导大鼠血中LPS浓度升高和肝缝织中LBP与CD14 mRNA的表达显著增强,增高的LBP和CD14 mRNA能增加肝脏对LPS的敏感性,可能造成肝脏损害.     

Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

Intestinal bacterial overgrowth and translocation, both common in cirrhosis with ascites, may lead to the activation of monocytes and lymphocytes, increased levels of proinflammatory cytokines, and enhanced synthesis of nitric oxide present in cirrhosis. Bacterial endotoxin promotes the synthesis of lipopolysaccharide (LPS)-binding protein (LBP), and forms a LPS-LBP complex that binds to CD14. This study was designed to evaluate LBP levels and their correlation to the immune response and the hemodynamic status in cirrhotic patients. Plasma LBP, endotoxin, soluble CD14 (sCD14), cytokines, renin, nitrites, and systemic vascular resistance were determined before and 4 weeks after norfloxacin or placebo in 102 cirrhotic patients and 30 controls. LBP was elevated in 42% of ascitic cirrhotic patients (15.7 +/- 0.7 versus 6.06 +/- 0.5 microg/mL, P <.01). In 60% of high LBP patients, endotoxin was within normal range. Among ascitic patients, those with high LBP showed greater (P <.05) levels of sCD14, tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), nitrites + nitrates (NOx)/creatinine, and renin, and lower vascular resistance. In the cirrhotic patients with high LBP, norfloxacin normalized (P <.01) LBP (from 16.6 +/- 0.5 to 5.82 +/- 0.8 microg/mL) and sCD14; reduced the level of cytokines, NOx/creatinine, and renin; and increased vascular resistance; but lacked effect in patients with normal LBP. Portal pressure was unchanged after norfloxacin in another group of 18 cirrhotic patients with high and 19 with normal LBP. In conclusion, the subset of ascitic cirrhotic patients with marked immune and hemodynamic derangement is identified by increased LBP levels. Amelioration of these abnormalities by norfloxacin suggests the involvement of enteric bacteria or their products in the triggering of the process.     

Utility of a new model to diagnose an alcohol basis for steatohepatitis

BACKGROUND & AIMS: Distinguishing an alcohol basis from a nonalcoholic basis for the clinical and histologic spectrum of steatohepatitic liver disease is difficult because of unreliability of alcohol consumption history. Unfortunately, various biomarkers have had limited utility in distinguishing alcoholic liver disease (ALD) from nonalcoholic fatty liver disease (NAFLD). Thus, the aim of our study was to create and validate a model to diagnose ALD in patients with steatohepatitis. METHODS: A cross-sectional cohort study was performed at the Mayo Clinic, Rochester, Minnesota, to create a model using multivariable logistic regression analysis. This model was validated in 3 independent data sets comprising patients of varying severity of steatohepatitis spanning over 10 years. RESULTS: Logistic regression identified mean corpuscular volume, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, body mass index, and gender as the most important variables that separated patients with ALD from NAFLD. These variables were used to generate the ALD/NAFLD Index (ANI), with ANI of greater than zero incrementally favoring ALD and ANI of less than zero incrementally favoring a diagnosis of NAFLD, thus making ALD unlikely. ANI had a c-statistic of 0.989 in the derivation sample, and 0.974, 0.989, 0.767 in the 3 validation samples. ANI performance characteristics were significantly better than several conventional and recently proposed biomarkers used to differentiate ALD from NAFLD, including the histopathologic marker protein tyrosine phosphatase 1b, AST/ALT ratio, gamma-glutamyl transferase, and carbohydrate-deficient transferrin. CONCLUSIONS: ANI, derived from easily available objective variables, accurately differentiates ALD from NAFLD in hospitalized, ambulatory, and pretransplantation patients and compares favorably with other traditional and proposed biomarkers.     

慢性重型肝炎患者血清内毒素调节蛋白的水平及其临床意义

探讨内毒素结合蛋白（lipopolysaccharide binding protein、LBP）、杀菌性／通透性增加蛋白（bactericidal/permeability-increasing protein、BPI）及可溶性sCD14(soluble CD14、sCD14)水平在慢重肝患者伴肠源性内毒素血症中的临床意义。应用基质显色法和ELISA双抗体夹心法，检测24例慢重肝患者血中内毒素脂多糖（Lipopolysaccharide,LPS)、LBP、BPI和sCD14的水平，并以10例献血员和16例慢性乙型肝炎患者作为对照。结果：慢重肝患者在早期、中期、晚期，其血中LPS、LBP、BPI和sCD14的水平均明显高于慢乙肝患者及献血员；慢重肝死亡者其LPS、LBP、BPI和sCD14的水平也显著高于存活者；慢重肝患者随着病情的加重，LBP／BPI比值增大。慢重肝患者伴肠源性内毒素血症时，高水平的LBP和sCD14及相对不足的BPI，可显著提高机体对LPS的敏感性。     

Regulation of interactions of endotoxin with host cells

Potent Toll-like receptor 4 (TLR4)-dependent cell activation by endotoxin requires lipopolysaccharide-binding protein (LBP) and CD14-dependent delivery of endotoxin to cells containing MD-2 and TLR4. We have used metabolically labeled [(14)C] meningococcal lipooligosaccharide (LOS), purified recombinant endotoxin-binding proteins, and cultured endothelial cells to better define protein:endotoxin intermediates key in cell activation in the absence of functional membrane (m) CD14. Protein:endotoxin complexes or aggregates (agg) were purified by gel sieving and characterized by immunocapture and bio-assays. Cell activation closely correlated with LBP, albumin and soluble (s) CD14-dependent conversion of endotoxin agg (M(r) > or = 20 x 10(6)) to monomeric (M(r) approximately 55 x 10(3)) endotoxin:sCD14 complexes. Ordered interaction of LBP (+ albumin) and sCD14 with LOSagg was required for the efficient formation of a bioactive endotoxin:sCD14 complex and potent cell activation. Increasing the ratio of LBP/sCD14 or addition of bactericidal/permeability-increasing protein (BPI) reduced accumulation of endotoxin:sCD14 complexes and instead yielded aggregates of endotoxin (M(r) approximately 1-20 x 10(6)) containing LBP or BPI that were taken up by cells in a CD14- and TLR4-independent manner without inducing pro-inflammatory responses. These findings strongly suggest that host machinery linked to TLR4-dependent cellular activation or TLR4-independent cellular clearance of endotoxin selectively recognizes different protein:endotoxin complexes. At the outset of infection, the low concentrations of LBP present and absence of extracellular BPI favor formation of pro-inflammatory endotoxin:CD14 complexes. The mobilization of LBP and BPI that is triggered by inflammation directs endotoxin for clearance and hence resolution of endotoxin-triggered inflammation.