坏死性胰腺炎对时某些粘附分子表达对中性粒细胞在肺脏聚集的影响

目的 探讨急性出血坏死性胰腺炎（ＡＮＰ）时中性粒细胞（ＰＭＮ）聚集了肺脏的机制。方法 在ＡＮＰ并发急性肺损伤（ＡＬＩ）模型，采用免疫组化技术等方法，动态观察ＡＮＰ后大鼠肺脏实质细胞细胞间粘附分子－１（ＩＣＡＭ－１）、ＰＭＮ表面巨噬细胞分化抗原－１（ＣＤ１１ｂ／ＣＤ１８）的表达改变和ＰＭＮ肺脏聚集的变化。结果 ＡＮＰ的肺脏ＩＣＡＭ－１表达逐渐增加，与ＰＭＮ肺脏聚集程度呈显著正相关，而ＰＭＮ表面ＣＤ１     

胃癌患者血清sICAM-1,sVCAM-1水平的研究

ＩＣＡＭ１（ＣＤ５４）和ＶＣＡＭ１均属于免疫球蛋白（Ｉｇ）超家族成员,其表达对炎性细胞因子ＩＬ１、ＩＦＮγ、ＴＮＦα的诱导高度敏感［１,２］。它们的配体分别为ＬＦＡ１（ＣＤ１１ａ）、ＭＡＣ１（ＣＤ１１ｂ）和ＶＬＡ４。ＩＣＡＭ１有５个...     

细胞间粘附分子—1与脑缺血再灌注损伤

细胞间粘附分子－１是在血管内皮细胞表达的免疫球蛋白超家族成员之一。它可以作为配基与白细胞表面表达的ＬＦＡ－１（ＣＤ１１ａ／ＣＤ１８）和Ｍａｃ－１（ＣＤ１１ｂ／ＣＤ１８）分子相结合,介导白细胞与血管壁内细胞的粘附及白细胞穿出血管壁,从而在脑缺血及脑缺血再灌注损伤中起到重要作用。     

肝星状细胞激活与ICAM-1的表达

目的探讨肝星状细胞（ＨＳＣ）的活化与细胞间粘附分子１（ＩＣＡＭ１）表达的关系．方法用链酶蛋白酶和胶原酶原位灌流，Ｎｙｃｏｄｅｎｚ密度梯度离心分离大鼠ＨＳＣ，并进行体外培养，应用免疫组织化学方法观察静息或活化状态下的ＨＳＣ中ＩＣＡＭ１表达．结果静息的ＨＳＣ不表达ＩＣＡＭ１，而活化的ＨＳＣ表达ＩＣＡＭ１，且随着培养时间的延长ＩＣＡＭ１表达量逐渐增加．结论ＩＣＡＭ１表达与ＨＳＣ活化及肝纤维化的发生有关．     

糖皮质激素受体对肾小球系膜细胞表达细胞间黏附分子-1的影响

近年来免疫病理学研究已经证实细胞间黏附分子１（ＩＣＡＭ１）作为细胞黏附分子中免疫球蛋白超家族成员之一,通过与炎性细胞表面同族型配体之间相互作用形成黏附,在免疫监督、炎症反应、吞噬过程、动脉粥样硬化等过程中起着重要的作用［１,２］。目前证实,肾小球系膜细胞（ＭＣ）表面低表达ＩＣＡＭ１,而细胞因子白细胞介素１β（ＩＬ１β）、肿瘤坏死因子α（ＴＮＦα）、干扰素γ（ＩＦＮγ）等刺激并上调系膜细胞表达ＩＣＡＭ１。本研究目的是进一步探讨糖皮质激素（ＧＣ）,如氟美松（Ｄｅｘ）对ＴＮＦα诱…     

高血压病人白细胞流变性与细胞粘附分子表达的变化

目的探讨白细胞流变性和细胞粘附分子（ＣＡＭＳ）表达与高血压发生及病情严重程度的关系。方法采用红细胞变形能力测定仪、体外血栓血小板粘附两用仪和酶联免疫吸附法（ＥＬＩＳＡ），检测１４９例高血压病人和１１０例健康人外周血白细胞变形能力（ＬＤ）、白细胞粘附功能（ＬＡＦ）、白细胞ＣＤ１８表达及血清可溶性细胞间粘附分子－１（ｓＩＣＡＭ－１）浓度的变化。结果高血压病人白细胞滤过指数（ＬＦＩ）、白细胞粘附率（ＬＡＲ）、白细胞ＣＤ１８表达和ｓＩＣＡＭ－１浓度均明显增高，与对照组比较差异有极显著性（Ｐ＜０．００１），三期病人各指标之间比较差异也具有极显著性（Ｐ＜０．００１），且以第３期病人各指标增高最明显。高血压病人ＬＡＲ与ＬＦＩ呈正相关（ｒ＝０．５７９，Ｐ＜０．００１）；ＬＡＲ和ＬＦＩ与白细胞ＣＤ１８表达和ｓＩＣＡＭ－１浓度呈正相关（ｒ＝０．６６２～０．８０４，Ｐ＜０．００１）。结论ＬＤ降低、ＬＡＦ及白细胞ＣＤ１８表达和ｓＩＣＡＭ－１浓度增高参与高血压的发生，且与病情严重程度有密切关系。     

抗ICAM-1和抗CD18单克隆抗体对兔实验性蛛网膜下腔出血后脑血管痉挛的缓解作用

研究发现，白细胞渗出参与了中枢神经系统的多种病理过程，包括蛛网膜下腔出血（ＳＡＨ）后脑血管痉挛的发生。细胞间粘附分子１（ＩＣＡＭ１）和整合素家族的共同β链（ＣＤ１８）是介导白细胞渗出的两个主要细胞因子。ＩＣＡＭ１由血管内皮细胞表达，是白细胞功能...     

干扰素对人甲状腺细胞表面抗原表达的影响

目的研究干扰素（ＩＦＮα、ＩＦＮγ）及激素对人正常甲状腺细胞表面抗原表达的影响,以探讨ＩＦＮα导致自身免疫性甲状腺病（ＡＩＴＤ）的可能机制。方法应用ＩＦＮα、ＩＦＮγ、促甲状腺激素（ＴＳＨ）及催乳素（ＰＲＬ）,刺激体外培养的来自６名正常人的甲状腺细胞,通过免疫荧光染色及流式细胞仪测定其表面抗原—ＨＬＡＤＲ、细胞间粘附分子１（ＩＣＡＭ１）、Ｂ７．１和甲状腺过氧化物酶（ＴＰＯ）的表达。结果（１）ＩＦＮα明显诱导甲状腺细胞表达ＩＣＡＭ１、Ｂ７．１和ＴＰＯ（分别为Ｐ＜０．０１、Ｐ＜０．０１、Ｐ＜０．０５）;（２）ＩＦＮγ明显诱导甲状腺细胞表达ＨＬＡＤＲ、ＩＣＡＭ１,但对Ｂ７．１的表达无促进作用（Ｐ＜０．０１、Ｐ＜０．０１、Ｐ＞０．０５）;（３）ＰＲＬ显著诱导甲状腺细胞表达ＩＣＡＭ１、Ｂ７．１和ＴＰＯ（Ｐ＜０．０５、Ｐ＜０．０１、Ｐ＜０．０１）。结论协同刺激信号对ＡＩＴＤ的发生起着关键作用。ＩＦＮα显著诱导甲状腺细胞表达协同刺激信号（Ｂ７．１）和自身抗原ＴＰＯ,可能是临床应用ＩＦＮα诱致ＡＩＴＤ的致病原因之一。ＰＲＬ在产后甲状腺炎发病和发展中的作用应予以关注     

硝苯地平对慢性支气管炎肺泡巨噬细胞上CD11c和CD14表达的影响

肺泡巨噬细胞（ＡＭ）为慢性支气管炎（慢支）气道内非特异性炎症反应的主要始动细胞［１］。脂多糖（ＬＰＳ）通过与ＡＭ上ＣＤ１１ｃ／ＣＤ１８和ＣＤ１４两种受体结合［１,２］,导致胞浆游离钙水平的升高,最终引起炎性介质的合成分泌,参与局部的炎症反应。而ＡＭ胞浆游离钙水平的升高又影响膜上ＣＤ１１ｃ／ＣＤ１８和ＣＤ１４两种受体的表达［３］。由于ＣＤ１８表达于所有细胞上,我们仅观察了硝苯地平在体外对ＬＰＳ诱导的ＡＭ胞浆游离钙水平变化及ＣＤ１１ｃ和ＣＤ１４表达的影响。对象与方法　１０例慢支缓解期患者经结合临床病…     

系统性红斑狼疮患者淋巴细胞粘附分子表达的观察

用流式细胞术及免疫双荧光染色法，分析了３５例系统性红斑狼疮（ＳＬＥ）患者外周血淋巴细胞粘附分子表型（ＣＤ＿（１１ａ）／ＬＦＡ－ｌα、ＣＤ＿（１８）／ＬＦＡ－１β、ＣＤ＿（５４）／ＩＣＡＭ－１）。结合淋巴细胞变化对ＳＬＥ作进一步探讨。结果发现ＳＬＥ活动期ＣＤ＿（１１ａ）、ＣＤ＿（１８）表达随ＣＤ＿４细胞减少而降低、ＣＤ＿８细胞增多而增高，ＣＤ＿（５４）在ＣＤ＿（２０）细胞上亦增高。此外，ＣＤ＿８细胞的ＣＤ＿（１８）增高与ＣＤ＿４ＣＤ＿（４５）ＲＡ￣＋细胞降低呈负相关（Ｐ＜０．０５），而与ＣＤ＿（２０）细胞的ＣＤ＿（５４）增高呈正相关（Ｐ＜０．０１）。提示粘附分子可能在ＳＬＥ发病机理中具有重要意义。     

Deep venous thrombosis: behaviour of the polymorphonuclear leukocyte integrin pattern at baseline and after in vitro activation

In a group of 18 subjects with acute deep venous thrombosis (DVT), evidenced by clinical examination and echo-color-Doppler, we examined the phenotypical expression of the polymorphonuclear leukocyte (PMN) beta2-integrins (CD11a, CD11b, CD11c, CD18), obtained by using a flow cytofluorimeter. The evaluation was performed before and after in vitro activation (prolonged for 5 and 15 minutes) with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). In DVT subjects, at baseline, the phenotypical expression of CD11b was decreased and that of CD11c was increased when compared with normal controls; no difference was found in CD11a and CD18 expression. In normal subjects PMN activation with both activators led to a constant increase of all PMN adhesion molecules; in DVT subjects CD11b, CD11c and CD18 increased, while CD11a expression did not show any change. These data indicate the presence of a functional alteration in circulating PMN cells from patients with DVT.     

Activation-dependent proteolytic degradation of polymorphonuclear CD11b

CD11b/CD18 is the principal integrin of polymorphonuclear (PMN) leucocytes and is involved in their adhesion, migration and phagocytosis. In quiescent cells, the receptor is stored in intracellular granules from where it is translocated to the cell surface in response to a variety of stimuli. In this study, we demonstrated that strong stimulation of PMNs not only leads to the upregulation of CD11b surface expression, but also to the subsequent time-dependent apparent loss of this receptor, as detected by fluorescence-activated cell sorting (FACS) using a monoclonal antibody (mAb) against an N-terminal CD11b epitope. This epitope loss was observed following either direct stimulation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (PMA) or after multiple receptor stimulation using a combination of the agonist N-formylmethionyl-leucyl-phenylalanine (FMLP) and the priming agents granulocyte macrophage-colony stimulating factor (GM-CSF) and platelet factor (PF) 4. However, upregulation following weak stimulation with FMLP alone was not followed by subsequent epitope loss of the receptor. The increases and subsequent decreases in CD11b expression induced by PMA were paralleled by an increase and a decrease in PMN adhesion to CD11b-specific ligands, fibrinogen and intercellular adhesion molecule (ICAM)-1. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis showed that this epitope loss of PMN CD11b was the result of proteolytic degradation of the N-terminal region of the molecule. The use of a range of proteinase inhibitors indicated that this CD11b degradation involves a cell-associated serine proteinase. This is the first demonstration of the proteolytic alteration of CD11b in response to strong PMN stimulation. Given the central role of CD11b/CD18 in all aspects of PMN function, this alteration of the CD11b molecule and its effect on PMN adhesion are probably of considerable pathophysiological importance.     

Polymorphonuclear leukocyte integrin profile in diabetes mellitus

We examined the polymorphonuclear leukocyte (PMN) integrin pattern in 45 diabetic subjects without macrovascular complications, including 21 subjects with type 1 and 24 with type 2 diabetes mellitus. The PMN adhesion molecules (CD11a, CD11b, CD11c, CD18) were evaluated using indirect immunofluorescence and a flow cytometer, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenyl-alanine (fMLP). At baseline, in diabetic subjects the phenotypical expression of CD11a and CD11b was significantly reduced and CD11c was increased, whereas CD18 was unchanged in comparison with normals. Considering type 1 and 2 diabetic subjects separately, CD11a was reduced and CD11c was increased in both subgroups, CD11b was decreased only in type 1 diabetics and CD18, decreased in type 1, was increased in type 2 subjects. After activation with PMA and fMLP, in normal subjects we observed a significant increase of all PMN adhesion molecules whereas in diabetic subjects only CD11c increased significantly with both activating agents, and CD11b increased only after PMA activation. In type 1 diabetic subjects only CD11c expression was increased, and in type 2 diabetic subjects an increase of CD11b (with PMA) and an increase of CD11c (with fMLP) were noted. In conclusion, we found in diabetic subjects of type 1 and 2 an altered behaviour pattern of PMN integrins both at baseline and, in particular, after in vitro activation. These data may help in explaining the role of PMN in the evolution of diabetic vascular complications.     

Alterations of Adhesion Molecule Expression and Inflammatory Mediators in Acute Lung Injury Induced by Septic and Non-septic Challenges

The lung is frequently the first failing organ during the sequential development of multiple organ dysfunction under both septic or non-septic conditions. The present study compared polymorphisms of tumor necrosis factor (TNFα), monocyte chemoattractant protein-1 (MCP-1), and adhesion molecule (AM) expression on circulating, recruited, and migrating leukocytes in the development of lung injury after induction of acute pancreatitis (AP) or abdominal sepsis by cecal ligation and puncture (CLP). Pulmonary alveolar barrier and endothelial barrier permeability dysfunction were measured. The expression of AMs (CD11b, CD11b/c, CD31, CD54 and CD62L) on leukocytes isolated from blood, lung tissue, and bronchoalveolar space were measured by flowcytometry. Plasma exudation to the interstitial tissue and the bronchoalveolar space significantly increased 1 and 3 hours after induction of pancreatitis and to the bronchoalveolar space from 6 hours after sepsis. Bronchoalveolar levels of MCP-1 significantly increased earlier than plasma exudation to the alveoli in both pancreatitis and sepsis. Alterations in expression of adhesion molecules on bronchoalveolar lavage (BAL) leukocytes can represent a marker reflecting leukocyte activation in the lung tissue, since both BAL and lung tissue leukocytes showed similar patterns of changes. Expression of adhesion molecules on circulating leukocytes increased 1 hour after induction of pancreatitis. Activating phenotypes of circulating, lung tissue and bronchoalveolar leukocytes may thus be responsible for the-development and severity of secondary lung injury.Supported by grants from the Swedish Research Council (grant no 11236), the Crafoord Foundation, Ake Wiberg Foundation, Maj Bergvall Foundation, Golje Foundation and Clas Groschinsky Foundation.     

Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins

Recruitment and activation of polymorphonuclear neutrophils (PMNs) reflects a primary immunological response to invading pathogens and has also emerged as a hallmark of vascular inflammation. One of the principal enzymes released upon PMN activation is myeloperoxidase (MPO), a heme protein that not only generates cytotoxic oxidants but also impacts deleteriously on nitric oxide-dependent signaling cascades within the vasculature. Because MPO also associates with the membrane of PMN, we evaluated whether MPO could also function as an autocrine modulator of PMN activation. The extent of PMN membrane-associated MPO was elevated in patients with acute inflammatory vascular disease compared with healthy individuals. Isolated PMNs bound free MPO by a CD11b/CD18 integrin-dependent mechanism. PMNs exposed to MPO were characterized by increased tyrosine phosphorylation and p38 mitogen-activated protein kinase activation. Also, nuclear translocation of NFkappaBin PMN was enhanced after incubation with MPO, as was surface expression of CD11b. Binding of PMN to MPO-coated fibronectin surfaces amplified PMN degranulation, as evidenced by increased release of MPO and elastase. MPO also augmented PMN-dependent superoxide (O(2)(*-)) production, which was prevented by anti-CD11b antibodies, but not MPO inhibitors. Collectively, these results reveal that binding of MPO to CD11b/CD18 integrins stimulates PMN signaling pathways to induce PMN activation in a mechanism independent of MPO catalytic activity. These cytokine-like properties of MPO thus represent an additional dimension of the proinflammatory actions of MPO in vascular disease.     

Polymorphonuclear leukocyte integrin profile in vascular atherosclerotic disease

Leukocyte-endothelial interactions could have a pathogenic role in atherogenesis. Adhesion molecules expressed by endothelial cells, such as intercellular adhesion molecule 1 (ICAM-1), interact with leukocyte integrins mediating the firm adhesion of leukocytes to endothelium which is followed by their transendothelial migration. The aim of our research was to evaluate polymorphonuclear leukocyte (PMN) integrin expression, at baseline and after activation, in a group of subjects with chronic vascular atherosclerotic disease (VAD). In 27 subjects with VAD we examined, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA), the PMN integrin pattern (CD11a, CD11b, CD11c, CD18) using indirect immunofluorescence and a flow cytometer. At baseline VAD subjects showed an increase of CD11a and CD18 and a decrease of Cd11b and Cd11c as compared to normal subjects. After activation, in normal subjects, we found an increase in the expression of all integrins, while in VAD subjects we observed an increase of CD11b and Cd11c and a decrease of Cd11a and CD18. In VAD subjects, at baseline, the upregulation of Cd11a and CD18 may reflect PMN in vivo activation; after in vitro activation, the decrease of CD11a may be related to the lack of cytoplasmic deposits of this molecule, while CD18 might be internalized. The integrin behaviour pattern in chronic VAD deserves further investigation, considering that integrins are potential targets of therapeutical strategies, with the aim of preventing the atherosclerotic plaque progression and acute ischaemic events.     

Graded experimental acute pancreatitis: monitoring of a renewed rabbit model focusing on the production of interleukin-8 (IL-8) and CD11b/CD18

OBJECTIVE: To establish and monitor a rabbit model of graded severity of acute pancreatitis to test the hypothesis that interleukin-8 (IL-8) and the adhesion molecule complex CD11b/CD18 are involved in the development of systemic complications in severe acute pancreatitis. METHODS: Acute pancreatitis induction in rabbits by duct ligation with or without infusion of 5.0% or 0.5% chenodeoxycholic acid or 0.9% saline. Control animals underwent laparotomy. The animals were monitored biochemically, histologically and immunohistochemically. RESULT: Increased serum levels of IL-8, tumour necrosis factor alpha (TNF-alpha), amylase and lipase were found in the chenodeoxycholic acid groups when compared with the saline, duct-ligated or control groups. Leukopenia, hypocalcaemia, and hyperglycaemia were marked in the 5.0% chenodeoxycholic acid group as compared to the saline, duct-ligated and control groups. Histologically, the 5.0% chenodeoxycholic acid group manifested a significant degree of pancreatic necrosis and neutrophil infiltration. The lungs of these animals showed acute lung injury and a significant up-regulation of CD11b/CD18. IL-8 was produced in pancreatic acinar and ductal cells. A significantly large output of ascitic fluid was seen in the 5.0% chenodeoxycholic acid group. CONCLUSION: The rabbit models of acute pancreatitis are reliable in that enzymatic and histological evidence of acute pancreatitis with or without systemic complications developed. IL-8 is produced locally in pancreatic acinar and ductal cells and significantly increased in peripheral blood during severe but not mild pancreatitis. The expression of the adhesion molecule complex CD11b/CB18 is significantly increased in lung tissue during severe acute pancreatitis with acute lung injury. IL-8 and CD11b/CB18 are involved in the pathogenesis of severe acute pancreatitis but not of mild oedematous pancreatitis.     

肿瘤坏死因子、白细胞介素8、可溶性细胞间粘附分子1和CD11b/CD18在良恶性胸腔积液的价值

目的 研究结核性及恶性胸腔积液患者及血清中肿瘤坏死因子（TNF）、白细胞介素－8（IL－8）、胸液中可溶性细胞间粘附分子1（sICAM-1）及外周血多形核白细胞（PMN）上粘附分子CD11d/CD18在参与胸膜病变的病理生理过程中的作用和在鉴别诊断上的价值。方法 采用放射免疫分析法（RIA法）、双抗体夹心ELISA法及流式细胞仪技术,检测31结核性、31例恶性胸腔积液患者胸液和（或）血清中TNF、IL－8、sICAM－1和CD11d/CD18表达水平,并与31例健康献血者对照。结果 结核性和恶性胸腔积液患者血清中TNF、IL－8含量以及PMN上CD11d/CD18表达显著高于正常对照组（P＜0．01）, 结核性胸液中TNF与IL－8水平和血PMN上CD11d/CD18表达明显高于恶性胸液患者（P＜0．01）,结核性胸粹中sICAM－1水平明显低于恶性胸液（P＜0．01）。胸腔积液中TNF与IL－8、sICAM－1水平呈显著正相关（r＝0．74和r＝0．79,P＜0．01）,血清TNF与PMN上CD11d/CD18的表达呈显著正相关（r＝0．61,P＜0．01）,胸腔积液中sICAM－1水平与血PMN上CD11d/CD18的表达呈显著负相关（经作曲线拟合,Y=1442．31－36．85X∧2＋0．25X∧2,R∧2＝0．59,F＝19．83,P＜0．01）。结论 细胞因子TNF、IL－8和粘附子sICAM－1、CD11b/CD18相互联系,在结核和肿瘤性胸膜病变的免疫 理生理过程中起着重要作用。它们在结核性和肿瘤性胸腔积液患者的表达水平不同,可作为临床上鉴别诊断的参考指标。     

beta(2)-Integrin blockade driven by E-selectin promoter prevents neutrophil sequestration and lung injury in mice

Interaction of CD11/CD18 beta(2) integrins on polymorphonuclear leukocytes (PMNs) with their counterreceptor, intercellular adhesion molecule-1, on the surface of vascular endothelial cells is a critical event mediating stable PMN adhesion and migration across the pulmonary vascular endothelial barrier. Neutrophil inhibitory factor (NIF), a 41-kDa glycoprotein isolated from the canine hookworm (Ancylostoma caninum), binds to the I domain of CD11a and CD11b and inhibits beta(2) integrin-dependent PMN adhesion. We describe a novel strategy using the endothelial cell-specific E-selectin promoter to induce NIF expression in an inflammation-specific manner in pulmonary vascular endothelial cells. A construct containing NIF cDNA driven by the inducible endothelial cell-specific E-selectin promoter (pESNIF) was transfected into human pulmonary artery endothelial cells (HPAECs). Lipopolysaccharide challenge (known to activate E-selectin) resulted in NIF mRNA and protein expression in transfected HPAECs. NIF expression induced by the E-selectin promoter prevented PMN adhesion to the activated HPAECs, whereas PMNs adhered avidly to activated HPAECs in the absence of NIF expression. To address the utility of this approach in conditionally preventing in vivo PMN sequestration, we injected mice intravenously with cationic liposomes containing the pESNIF construct. Analysis of lung tissue showed that intraperitoneal challenge of Escherichia coli resulted in NIF expression. Inflammation-specific NIF expression induced by the E-selectin promoter prevented lung PMN sequestration and vascular injury induced by E coli challenge. These studies suggest the feasibility of conditionally blocking beta(2) integrin function at sites where the endothelium is activated and thereby of locally preventing PMN activation and migration responses that lead to tissue inflammation.     

Acute Ethanol Intoxication Inhibits Neutrophil β2-Integrin Expression in Rats During Endotoxemia

The effects of acute ethanol intoxication on neutrophil [polymorphonuclear leukocyte (PMN)] adhesion molecule expression and certain other functional properties during endotoxemia were studied in rats to elucidate the mechanisms underlying the immunosuppressive effects of ethanol. Acute ethanol intoxication was induced by an intraperitoneal injection of 20% ethanol at a dose of 5.5 g of ethanol/kg. Control animals received an intraperitoneal injection of saline. Thirty minutes after intraperitoneal injection, animals were given a 90-min intravenous infusion of Escherichia coli endotoxin (total dose of 112.5 μg/rat in 2.5 ml of saline) or saline. Certain rats received granulocyte colony-stimulating factor (G-CSF; 50 μg/kg in 5% dextrose, subcutaneous injection twice daily) or vehicle pretreatment for 2 days before intravenous endotoxin infusion. Endotoxemia significantly upregulated CD11b/c and CD18 expression on PMNs when compared with those of saline-infused rats. Acute ethanol intoxication inhibited this endotoxin-induced upregulation of CD11b/c and CD18 expression on PMNs. Ethanol intoxication also suppressed the phagocytic activities of PMNs in saline-infused rats, but this suppression failed to reach statistical significance in endotoxin-infused rats. Hydrogen peroxide generation by PMNs in saline- or endotoxin-infused rats was not affected by ethanol intoxication. Histological examination showed extensive PMN sequestration in the liver after endotoxin infusion, and ethanol intoxication significantly attenuated this hepatic sequestration of PMNs. G-CSF pretreatment enhanced neutrophil phagocytosis, CD11b/c and CD18 expression in endotoxin-infused rats, and prevented the ethanol-induced inhibition of neutrophil CD18 expression and phagocytosis. The impairment of β₂-integrin expression on PMNs may be one mechanism underlying ethanol-induced defects of neutrophil delivery into tissue sites of infection. G-CSF may be of benefit to the infected alcoholic host by enhancing leukocyte defense functions.