人血浆高密度脂蛋白对大鼠内毒素血症的治疗及预防作用研究

目的观察人血浆高密度脂蛋白(HDL)对大鼠内毒素血症的治疗和预防效果.方法实验分为对照组、治疗组和预防组.对照组(n=10)仅静脉输注内毒素(ET,500EU/kg);治疗组(n=8)先静脉输注ET,待血压明显下降及ET输注后1h,再静脉输注HDL(75mg/kg);预防组(n=8)输注HDL后再输注ET.分别在3个不同时点,即第1时点(输注ET或HDL前,为自身正常对照)、第2时点(ET输注后1h)和第3时点(ET输注后2h)静脉采血,采用鲎试剂法和放射免疫分析法测定大鼠血浆ET水平和肿瘤坏死因子(TNF)浓度并观察血压及存活时间.结果(1)输注ET后对照组大鼠血压进行性下降(P＜0.01);输注HDL后治疗组大鼠血压下降程度明显弱于对照组(P＜0.01);预防组大鼠输注ET后其血压无明显下降(P＞0.05).治疗组及预防组大鼠存活时间均较对照组明显延长(P＜0.01).(2)3组大鼠血浆ET水平在各时点均无明显差异(P＞0.05).(3)无论是治疗组还是预防组,其血浆TNFα水平于第3时点均明显降低(P＜0.05).结论人血浆HDL能减轻或抑制内毒素血症大鼠血压的下降并明显延长其存活时间,说明人血浆HDL能提高机体对抗ET损伤的能力,对内毒素血症具有较理想的治疗和预防作用;人血浆HDL拮抗ET损伤的机理可能与其抑制TNF释放有关.     

人血浆天然高密度脂蛋白在内毒素休克中的治疗作用研究

为探讨人血浆天然高密度脂蛋白(HDL)在内毒素休克中的治疗效果,采用大鼠内毒素休克模型,观察大鼠血压、存活时间、内毒素、TNF等指标的变化.结果表明,输注HDL可明显提高内毒素休克大鼠的血压(P<0.01)、延长大鼠的存活时间(P<0.01)并降低血浆TNF水平(P<0.05).结果提示人血浆天然HDL不但可以抑制TNF的释放,而且还能提高机体对抗内毒素的能力,对内毒素休克具有较理想的治疗作用.     

重组人生长激素对内毒素血症大鼠的治疗作用

目的 :观察重组人生长激素 (rhGH)对大鼠内毒素血症的治疗效果。方法 :76只SD大鼠随机分为正常对照组、内毒素血症组 (仅腹腔注射鸵鸟株大肠杆菌 (1 5ml/kg ,1× 1 0 10 cfu/L)及治疗组 (腹腔注射鸵鸟株大肠杆菌后行rhGH肌肉注射 (2 2 5IU/kg/d)。内毒素血症组及治疗组又依观察时点再分为 1天、3天两个亚组。采用放射免疫分析方法测定血浆肿瘤坏死因子 α(TNF α)浓度并观测大鼠血压的变化。结果 :与正常对照组相比 ,无论是内毒素血症组还是治疗组 ,1天时其大鼠血浆TNF α浓度均明显升高 (P <0 .0 5 ) ;虽然两组大鼠血压都降低 (P <0 .0 5 ) ,但治疗组大鼠血压降低幅度明显小于内毒素血症组 (P <0 .0 0 1 )。 3天时 ,内毒素血症组大鼠血浆TNF α浓度降至正常对照水平 ,而治疗组大鼠血浆TNF α浓度却明显低于正常对照组 (P <0 .0 0 1 )及内毒素血症组 3天水平 (P <0 .0 5 )。结论 :rhGH能明显减轻内毒素血症大鼠血压的下降 ,对内毒素血症大鼠具有较理想的治疗效果 ;rhGH减轻血压下降的机制可能与其能抑制TNF的释放等有关     

L-苯丙氨酸对自发性高血压大鼠血液NO、ET和SOD水平的影响

目的： 探讨苯丙氨酸对自发性高血压大鼠(SHR)血浆NO、ET和SOD水平的影响。方法: 以11只4周龄雄性SHR 为实验对象,分为苯丙氨酸饲喂组（n=6）及对照组（n=5）;另以相同周龄的WKY大鼠（n=6）作为正常对照组。至实验大鼠30和42周龄时，检测血浆NO、ET和SOD的水平。结果: SHR血浆NO水平明显高于WKY (P<0.01)，血浆ET水平明显低于WKY (P<0.01)；苯丙氨酸治疗后抑制SHR血压的上升，血浆SOD及ET水平明显上升(P<0.01)；血浆NO水平明显下降(P<0.01)。结论: 苯丙氨酸可调节氧自由基的清除和改善内皮细胞的内分泌功能，这可能是苯丙氨酸新的降低血压的机制。     

三种温病治法制剂干预家兔内毒素血症疗效特点的比较研究

目的比较及分析清热解毒、活血化瘀和养阴增液三种温病治法制剂抗内毒素效应的特点。方法以大肠杆菌内毒素EColiO111B4 静脉注射建立家兔内毒素血症模型 ,并随机分为模型对照组、清热解毒组、活血化瘀组、养阴增液组 ,后三组动物分别给予相应治法的注射液进行干预 ,另设正常对照组。采用动态比浊鲎试验法定量检测血浆内毒素 (EXT)浓度 ;常规计数血白细胞(WBC)、血小板 (PLT)及检测凝血酶原时间 (PT)、凝血酶时间(TT) ,以放射免疫分析法检测血清肿瘤坏死因子 -α(TNF -α)、白细胞介素 -1β(IL -1β)、内皮素 -1(ET -1)以及前列环素(PGI2)水平。结果与模型对照组比较 ,各治疗组血浆内毒素水平无显著性差异 ,但三治疗组血清中由内毒素诱生的炎性细胞因子水平和血管活性介质均有不同程度的改善。清热解毒组家兔血清TNF -α、IL -1β 降低最为显著 (均P<0.01) ,活血化瘀组改善ET -1、PGI2 最为明显 (分别为P<0.05 ,P<0.01) ,而养阴增液组前两者的功效兼而有之。结论三种温病治法制剂均具有一定的抗内毒素效应 ,但其治疗内毒素血症的作用环节及机理方面各具特点 ,从而显示中医治疗温病采用多种治法配伍的合理性     

急性肝衰竭时肠源性内毒素血症对肝脏能量代谢的影响

目的:研究急性肝衰竭时肠源性内毒素血症对肝脏能量代谢的影响。方法:以硫代乙酰胺(TAA)染毒建立急性肝损伤大鼠模型;应用酶荧光法测定动脉血酮体(乙酰乙酸、β-羟基丁酸)浓度及肝细胞线粒体ATP含量;采用结肠切除术并观察血浆内毒素水平与血清丙氨酸氨基移换酶(ALT)活性的变化。结果:TAA组大鼠血浆内毒素水平与血清ALT活性均显著高于正常对照组(P＜0.01),动脉血酮体比(AKBR)降至0.4以下,动脉血中总酮体浓度显著低于正常对照组(P＜0.01)。切除结肠的TAA染毒组大鼠未发生内毒素血症,肝细胞线粒体ATP含量显著高于TAA组(P＜0.01),血清ALT活性虽高于正常对照组(P＜0.05),但显著低于TAA组(P＜0.01)。结论:肠源性内毒素血症可损伤肝脏能量代谢,使肝脏代谢和功能发生严重障碍,在急性肝衰竭的发生过程中具有关键性作用。     

葡萄糖调节蛋白78在复合致病因素诱导的大鼠肝肺综合征中的作用

目的: 探讨葡萄糖调节蛋白78(GRP78)在大鼠肝肺综合征发病中的作用及其与肠源性内毒素血症的关系。方法: Wistar大鼠被随机分为4周组、6周组和8周组3个时点,采用复合致病因素法制备大鼠肝硬化合并肝肺综合征(HPS)模型,并设标准饮食的正常大鼠作为对照组。采用HE染色观察肺组织病理变化;测定血浆中丙氨酸氨基转移酶(ALT)、内毒素、TNF-α和肺组织匀浆中的TNF-α、丙二醛(MDA)的含量。Western blotting和RT-PCR法检测肺组织标本中GRP78蛋白和mRNA表达水平。结果: 模型组动物血浆内毒素含量随病程进展逐渐增高;肺组织中GRP78蛋白和mRNA的表达随HPS进展逐步增高,且各时点间的表达有显著差异(P<0.05);血浆内毒素与升高的GRP78蛋白水平间呈高度正相关(P<0.01)。血浆ALT和TNF-α含量以及肺组织匀浆中TNF-α和MDA含量随病程进展逐渐增高;血浆内毒素含量以及肺组织中GRP78蛋白分别与血浆TNF-α和肺组织中TNF-α、MDA的含量呈高度正相关(P<0.01)。在各时点,模型组动物血浆TNF-α含量、肺组织匀浆TNF-α、GRP78蛋白及mRNA均显著高于正常对照组(P<0.05)。在第6周和第8周,模型组动物血浆内毒素和ALT的含量以及肺组织匀浆中MDA的含量均显著高于正常对照组(P<0.05)。结论: 肝硬化时形成的肠源性内毒素血症作为内质网应激的重要应激原,通过氧化应激激活肺组织的内质网应激反应导致GRP78表达增高,很可能是HPS发病的重要机制。     

重组人生长激素对败血症大鼠的实验治疗

目的:观察重组人生长激素(rhGH)对败血症大鼠的治疗效果并探讨其作用机制。方法:观测正常对照组、败血症组及败血症+rhGH组大鼠平均动脉压(MAP)、白细胞计数、血浆TNFα、IL-1β和内毒素(ET)水平及1周存活率。结果:(1)rhGH能明显减轻败血症大鼠MAP的下降、降低血浆TNFα及ET水平并提高其中性粒细胞比例;rhGH能显著提高败血症大鼠1周存活率。(2)各组血浆IL-1β浓度在各时点均无明显变化。结论:rhGH对败血症大鼠具有较理想的治疗效果, 其机制可能与rhGH改善败血症大鼠的循环功能障碍、保护肠粘膜屏障、减轻肠道细菌/ET移位及抑制TNFα的生成和释放等有关。     

iNOS-GC-cGMP信号活化参与了内毒素血症大鼠血管低反应性的发生机制

目的: 探讨诱导型一氧化氮合酶(iNOS)-鸟苷酸环化酶(GC)-环磷酸鸟苷(cGMP)信号活化在内毒素血症大鼠血管低反应中的作用。方法: 采用腹腔注射脂多糖(LPS)诱导大鼠内毒素血症模型,24只SD大鼠随机分为假手术组(sham组)、内毒素血症组(LPS组)、内毒素血症+多黏菌素B组(LPS +PMX-B组)和多黏菌素B组(PMX-B组)。颈总动脉插管记录大鼠平均动脉血压(MABP);检测各组大鼠血清中NO、iNOS和TNF-α的水平;用离体血管灌流方法,生物信号处理系统测定大鼠胸主动脉环的张力。结果: 与sham组相比,LPS组大鼠MABP显著降低(P<0.01),LPS+PMX-B组大鼠明显高于LPS组(P<0.05),而PMX-B组与sham组比无统计学意义(P>0.05);生化检测发现LPS组大鼠血浆中NO、iNOS以及TNF-α水平显著高于sham组和LPS+PMX-B组(P<0.01)。同sham组相比,LPS组大鼠离体胸主动脉环对去氧肾上腺素(Phe)刺激的收缩反应及其对乙酰胆碱(ACh)的舒张反应均明显低下(P<0.01);与LPS组相比,LPS+PMX-B组的反应明显改善(P<0.01);氨基胍(AMG)预处理后,同sham组和PMX-B组相比,LPS组与LPS+PMX-B大鼠离体胸主动脉环对Phe(10^-7~10^-5 mol·L^-1)诱导下的各组血管环的收缩反应明显改善(P<0.05或P<0.01);亚甲蓝(MB)预处理后,同sham组和PMX-B组相比,LPS组与LPS+PMX-B组大鼠离体胸主动脉环对Phe(10^-7~10^-5 mol·L^-1)诱导下的各组血管环的收缩反应均得到改善(P<0.05或P<0.01);PMX-B组与sham组比差异无统计学意义(P>0.05)。结论: iNOS-GC-cGMP信号活化参与了内毒素血症大鼠血管低反应性;多黏菌素B改善内毒素血症大鼠血管低反应性,可能与中和内毒素、减少炎症因子释放、抑制iNOS-GC-cGMP信号活化有关。     

家兔内毒素血症时肝肾心肺线粒体磷脂酶A_2及其膜流动性的改变

本研究采用家兔内毒素休克模型,实验分为四组:对照组;内毒素血症组;磷酸氯喹(CQ)预处理组;地塞米松(DXM)预处理组,测定血浆和肝、肾、心、肺线粒体PLA_2活性及线粒体膜流动性。结果表明正常对照和注射内毒素(ET)后1、3、5、8h血浆PLA_2分别为15.52±5.31与25.83±7.86、30.54±11.53、37.13±8.53、41.88±7.32U/ml,注射ET后血浆PLA_2显著高于注射前(P<0.05)。CQ、DXM预处理组则血浆PLA_2显著低于内毒素血症动物(P<0.05)。注射ET8h后肝、肾、心、肺线粒体PLA_2活性显著高于正常对照组。而CQ、DXM预处理组显著低于内毒素血症组(P<0.05)。同时内毒素血症组肝、肾、心、肺线粒体膜流动性降低,分子排列有序性升高,膜脂区微粘度升高;而CQ、DXM预处理组肝、肾、心、肺线粒体膜流动性显著改善。线粒体PLA_2升高和膜流动性降低呈显著正相关。     

封闭枯否细胞和脾切除对急性肝损伤影响的实验性研究

目的:探讨封闭枯否细胞与脾切除对肠源性内毒素血症形成及肝实质细胞损伤的影响。方法:采用硫代乙酰胺(TAA)给大鼠灌胃,同时分别采用GdCl₃封闭枯否细胞及脾脏切除作为实验组,观察吞噬指数、ALT、TNF-α、内毒素等指标。结果:GdCl₃封闭及脾脏切除组吞噬指数下降,内毒素水平明显升高(P<0.05),TNF-α水平减少(P<0.05),ALT、TB水平明显下降(P<0.05)。结论:抑制枯否细胞功能与脾切除均可使肠源性内毒素水平升高,由于分泌功能同时受到抑制,使TNF-α水平下降,肝损伤减轻。     

糖调节蛋白78在大鼠肠源性内毒素血症促进肝硬化形成中的作用

目的:探讨糖调节蛋白78(GRP78)在大鼠肠源性内毒素血症(IETM)促进肝硬化形成过程中的作用。方法:51只雄性Wistar大鼠随机分为肝硬化模型4周组、6周组、8周组及同期正常对照组。采用复合致病因素法诱导大鼠肝硬化,HE染色和VG染色分别观察肝损伤和肝纤维化情况;RT-PCR法和免疫组化法分别检测肝组织GRP78 mRNA及蛋白表达;同时测定血浆中丙氨酸氨基转移酶(ALT)、内毒素、肿瘤坏死因子-α(TNF-α)、同型半胱氨酸(HCY)以及肝组织匀浆中TNF-α、丙二醛(MDA)、Ⅲ型前胶原(PⅢP)水平。结果:(1)随病程进展,各模型组血浆中ALT、内毒素、TNF-α、HCY以及肝组织中GRP78 mRNA、蛋白表达水平、MDA、TNF-α、PⅢP含量和肝组织纤维化指数均逐渐升高并显著高于正常对照组(P0.05)。(2)血浆中升高的内毒素水平分别与GRP78蛋白、血浆MDA和HCY水平以及肝纤维化指数呈显著正相关(P0.01);表达增高的GRP78蛋白分别与血浆MDA和HCY水平以及肝纤维化指数呈显著正相关(P0.01)。结论:GRP78可能在肝硬化形成过程中发挥重要作用;内质网应激很可能是IETM促进肝纤维化乃至肝硬化发生的重要机制。     

Similar cytokine but different coagulation responses to lipopolysaccharide injection in D-galactosamine-sensitized versus nonsensitized rats.

To compare cytokine release and coagulation disturbances induced by administration of high versus low doses of endotoxin (lipopolysaccharide [LPS]), we used two endotoxin test systems similar in mortality but different in the degree of endotoxemia. One group of rats (n = 11) randomly received endotoxin (15.0 mg/kg of body weight intraperitoneally [i.p.]) and 1 ml of Ringer's solution (nonsensitized animals). The second group (n = 11) received 1 ml of D-galactosamine (500 mg/kg i.p.) and endotoxin (100 micrograms/kg i.p.) simultaneously (sensitized animals). Endotoxin levels in the plasma of nonsensitized rats were 1,000-fold higher than those in the plasma of sensitized rats (69.33 x 10(3) +/- 22.42 x 10(3) versus 75.8 +/- 27.08 ng of LPS per ml), leading to a mortality of 91% in nonsensitized rats versus 82% in the sensitized-rat model within 48 h postendotoxemia. Serum transaminase activity increased up to 100-fold in sensitized rats as a sign of hepatocyte damage. Despite the large difference in LPS levels in plasma, the time courses of the plasma tumor necrosis factor (TNF) increase were similar in the two groups, with a peak at 2 h (54 +/- 12 ng/ml in nonsensitized rats versus 43 +/- 12 ng/ml in sensitized rats), and also similar to that of a group of nonsensitized rats (n = 5) that received a low dose of LPS (100 micrograms/kg) only (52 +/- 21 ng/ml), while D-galactosamine alone did not induce TNF release. Despite similar TNF levels, a more pronounced coagulation disorder was observed at 4 h in nonsensitized rats (with the high LPS dose) as measured by platelet counts, plasma fibrinogen levels, and activated partial thromboplastin time prolongation (191 x 10(3) +/- 107 x 10(3) cells per microliter, 40 +/- 24 mg/dl, and 53 +/- 15 s, respectively) than in rats with the low LPS dose either sensitized (495 x 10(3) +/- 153 x 10(3), 95 +/- 49, and 38 +/- 16, respectively) or nonsensitized (439 x 10(3) +/- 62 x 10(3), 170 +/- 18, and 35 +/- 11, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)     

内毒素致兔肝线粒体膜磷脂含量改变及阳离子A的拮抗效应

目的： 采用内毒素血症兔实验模型，研究肝线粒体膜磷脂含量的改变及阳离子A的拮抗效应。方法: 将48只日本大耳白兔随机分为正常对照组(Ⅰ组)、内毒素组(Ⅱ组)和阳离子A拮抗组(Ⅲ组)。3组同时进行相应处理后，分别在第3、7 h 测定各组肝线粒体膜中磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)、磷脂酰丝氨酸(PS)和磷脂酰肌醇(PI)的含量变化。结果: Ⅱ组中PC、PE、PS、PI含量在第 3 h、7 h 均低于Ⅰ组，差异极显著(P<0.01)；而Ⅲ组中4种磷脂的含量在第 3 h、7 h 又均高于Ⅱ组(P<0.05, P<0.01)。结论: 内毒素致使兔肝线粒体膜磷脂含量降低，而阳离子A一定程度上具有对内毒素的拮抗作用和对肝线粒体膜的保护效应。     

Effect of Salvia Miltiorrhizae on the Expressions of TLR4 Protein in the Liver of Rats with SAP or OJ

To investigate the effect of salvia miltiorrhizae on the expressions of TLR4 protein in the liver of rats with severe acute pancreatitis (SAP) and obstructive jaundice (OJ), and explore the protective mechanism of salvia miltiorrhizae on the liver of rats. A total of 288 mice was used in SAP- (n = 108) and OJ-associated experiments (n = 180). The rats were randomly divided into sham-operated, model control and treated group. Based on the different time points after operation, these groups were subdivided into 3, 6 and 12 h subgroups (SAP rats, n = 12) or 7, 14, 21 and 28 days subgroups (OJ rats, n = 15). At the corresponding time points after operation, blood and liver specimens were collected to determine the contents of endotoxin and TNF-α in the blood as well as the expression levels of TLR4 protein in the liver. Compared with the corresponding model control group, though the number of dead SAP or OJ rats in the treated group declined, no statistical difference was noted; The levels of plasma endotoxin in SAP (at 6 and 12 h) or OJ rats in the treated group decreased significantly (P < 0.001 and P < 0.01, respectively); The levels of serum TNF-α in SAP (at 12 h) or OJ rats (on 14 days) declined (P < 0.001 and P < 0.01, respectively); The staining intensity as well as the product of staining intensity and positive rate of TRL4 protein only significantly declined on 7 and 28 days in OJ rats (P < 0.01). On 7 days, treated group in positive rate of TLR4 protein were significantly lower than that in model control group (P < 0.01). The pathological changes in different treated groups of SAP and OJ rats were improved. Salvia miltiorrhizae is able to reduce the levels of plasma endotoxin and inhibit effectively the expressions of TLR4 protein in the liver of SAP or OJ rats, thereby decreasing inflammatory reaction and exerting protective effect on liver function. We claimed that this paper was original and would not have any financial interest in a company or its competitor, and that all authors meet criteria for authorship. We abided the ethics in this animal experiment study. The ethics committee approval of our hospital and Zhejiang Univeristy were secured for the animal study reported, and all rats have not been abused and executive mercy killing when the observing time in this study was over.     

三种温病治法制剂干预家兔内毒素血症疗效特点的比较研究

目的 :比较及分析清热解毒、活血化瘀和养阴增液三种温病治法制剂抗内毒素效应的特点。方法 :以大肠杆菌内毒素EColiO1 1 1 B4静脉注射建立家兔内毒素血症模型 ,并随机分为模型对照组、清热解毒组、活血化瘀组、养阴增液组 ,后三组动物分别给予相应治法的注射液进行干预 ,另设正常对照组。采用动态比浊鲎试验法定量检测血浆内毒素 (EXT)浓度 ;常规计数血白细胞 (WBC)、血小板 (PLT )及检测凝血酶原时间 (PT)、凝血酶时间 (TT ) ,以放射免疫分析法检测血清肿瘤坏死因子 α(TNF α)、白细胞介素 1β(IL 1β)、内皮素 1(ET 1)以及前列环素 (PGI2 )水平。结果 :与模型对照组比较 ,各治疗组血浆内毒素水平无显著性差异 ,但三治疗组血清中由内毒素诱生的炎性细胞因子水平和血管活性介质均有不同程度的改善 ;清热解毒组家兔血清TNF α、IL 1β降低最为显著 (P均 <0 .0 1) ;活血化瘀组改善ET 1、PGI2 最为明显 (分别为P <0 .0 5,P <0 .0 1) ;而养阴增液组前两者的功效兼而有之。结论 :三种温病治法制剂均具有一定的抗内毒素效应 ,但其治疗内毒素血症的作用环节及机理方面各具特点 ,从而显示中医治疗温病采用多种治法配伍的合理性     

内源性高甘油三酯血症患者血浆VLDL、LDL及HDL对血凝的影响

目的：研究内源性高甘油三酯血症(HTG)患血浆极低密度脂蛋白(VLDL)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL)是否发生了氧化修饰及其对血凝的影响。方法：对2l例内源性高甘油三酯血症患与2l例年龄性别相近的正常人的血脂、脂质过氧化物进行了分析。用一次性密度梯度超速离心法分离血浆VLDL、LDL及HDL，测定这三种脂蛋白的234nm光吸收、相对电泳迁移率(REM)和硫代巴比妥酸反应物质(TBARS)，分别将这三种脂蛋白加入由正常人新鲜混合血浆构成的反应系统中，按试剂盒分别测定凝血酶原时间(PT)及活化部分凝血酶原时间(APIT)。结果：内源性HTG患血浆TG含量平均升高2．73倍，HDLC下降l.7l倍，同时LPO升高1．22倍;HTG组VLDL、LDL及HDL的REM、234nm光吸收值、TBARS含量均较对照组显增加(P＜0．01)，表明内源性HTG患血浆VLDL、LDL及LDL均发生了氧化修饰生成Ox—VLDL、Ox-LDL.PT及APTT在分别加入HTG组的VLDL、LDL及HDL后均比加入相应正常组脂蛋白明显缩短(P均＜0．05)。相关分析表明，HTG组血浆VLDL及HDL相对电泳迁移率(REM)与PT呈负相关(P＜0．01)。结论：HTG患血浆VLDL、LDL及HDL发生了氧化修饰，并使PT及APTT明显缩短。     

Inhibition of pulmonary neutrophil trafficking during endotoxemia is dependent on the stimulus for migration

In rat models of Gram-negative pneumonia, pulmonary emigration of neutrophils (polymorphonuclear leukocytes [PMNs]) is blocked when rats are made endotoxemic by an intravenous administration of endotoxin (lipopolysaccharide [LPS]). To test whether dysfunctional PMN migratory responses in the endotoxemic rat are specific for airway endotoxin, we gave rats intrapulmonary stimuli known to elicit different adhesion pathways for pulmonary PMN migration. Sprague-Dawley rats were treated intravenously with either saline or LPS and then instilled intratracheally with either sterile saline, LPS from Escherichia coli, interleukin (IL)-1, hydrochloric acid (HCl), zymosan-activated serum (ZAS), or lipoteichoic acid (LTA). Three hours later, accumulation of PMNs and protein in bronchoalveolar lavage fluid (BALF) were assessed. BALF PMN accumulation in response to intratracheal treatment with LPS (100%), IL-1 (100%), ZAS (40%), and LTA (58%) was inhibited by endotoxemia. In rats given intratracheal HCl, BALF PMN numbers were unaffected by intravenous LPS. The pattern of inhibition of migration suggests that intravenous LPS only inhibits migration in response to stimuli for which migration is CD18-dependent. In contrast to PMN migration, BALF protein accumulation was inhibited by intravenous LPS only when IL-1 or LPS was used as the intratracheal stimulus. To characterize further the differential responses to the various airway stimuli, the appearance in BALF of tumor necrosis factor-alpha (TNF-alpha) and the PMN chemokine macrophage inflammatory protein (MIP)-2 was measured. Accumulation of PMNs in BALF correlated with the BALF concentrations of MIP-2 (r = 0.846, P < 0.05) and TNF (r = 0.911; P < 0.05). The ability of intravenous LPS to inhibit pulmonary PMN migration correlated weakly with MIP-2 (r = 0.659; P < 0.05) and with TNF (r = 0.413; P > 0.05) concentrations in BALF. However, this correlation was strengthened for TNF (r = 0.752; P < 0.05) when data from IL-1-treated animals were excluded. Thus, the presence in BALF of inflammatory mediators that are known to promote CD18-mediated migration correlates with endotoxemia-related inhibition of PMN migration. Furthermore, the pattern of inhibition of pulmonary PMN migration during endotoxemia is consistent with the CD18 requirement of each migratory stimulus.