Chemoattractant-induced firm adhesion of leukocytes to vascular endothelium in vivo is critically dependent on initial leukocyte rolling

Leukocyte rolling and firm adhesion at the venular endothelium are two discrete events in the cellular inflammatory response mediated via selectin and integrin adhesion molecules, respectively. The dependency of chemoattractant-induced firm leukocyte adhesion on the preceding rolling interaction was investigated in rat mesenteric microvessels through use of intravital microscopy. Leukocyte rolling was dose-dependently inhibited by systemic treatment with the sulphated polysaccharide fucoidin. The firm leukocyte adhesion following stimulation with the chemotactic peptide fMLP was similarly inhibited when fMLP challenge was performed subsequent to inhibition of leukocyte rolling by fucoidin. Thus, based on paired observations in single venules before and after fucoidin treatment, reduced rolling leukocyte flux prior to fMLP challenge was paralleled over a wide range by a proportional decrease in fMLP-induced leukocyte adhesion. The results demonstrate quantitatively a close relationship between the extent of leukocyte rolling and the magnitude of the subsequent firm adhesion response, and, that an initial rolling interaction is a precondition for firm adhesion to occur at physiological blood flow rates in vivo.     

Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in experimental allergic encephalomyelitis

Anti-tumor necrosis factor (TNF) antibodies inhibit passively transferred experimental allergic encephalomyelitis (EAE) in SJL mice. The possibility that this occurs through interference in TNF's upregulation of endothelial cell adhesion molecules was investigated. Expression of both vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on spinal cord vessels increased during EAE. The upregulation of VCAM-1 was markedly reduced or prevented by anti-TNF treatment. Leukocytic infiltration was 15-fold lower in anti-TNF-treated than diseased animals. Spinal cord endothelial expression of VCAM-1, though not ICAM-1 or fibronectin, positively correlated with the extent of T cell, B cell or monocyte infiltration in each animal.     

Selective vessel ligation in the pelvis: an invaluable tool in certain surgical procedures

While developing the technique of abdominal radical trachelectomy for conservative cervical cancer management, the vascular supply of the uterus was thoroughly examined. The question of how many vessels the uterus requires to ensure its viability arose. Following an abdominal radical trachelectomy for stage IB cervical carcinoma, blood supply of the body of the uterus is successfully maintained by only the two infundibulopelvic vessels (n= 34). Pregnancy has resulted following this technique (n= 2). Selective ligation of the pelvic vasculature has been utilized in the abdominal radical trachelectomy procedure. The objectives of this study were to investigate the vasculature of the infundibulopelvic and broad ligaments, to assess the contribution of the ovarian and uterine vessels to overall uterine perfusion, and to consider the clinical applications of selective pelvic vessel ligation. Ten fresh dissections of the infundibulopelvic vessels, broad ligaments of benign total abdominal hysterectomy, and bilateral salpingo-oophorectomy specimens were performed. Perfusion index (PI) and oxygen saturation (O(2)Sat) measurements using a modified probe were taken at specified intervals at the uterine cornu during ten routine benign abdominal hysterectomies to assess the contribution of the ovarian and uterine vessels to overall uterine perfusion and the concepts studied were utilized in certain gynecological procedures. The ovarian/infundibulopelvic vessels course medially through the broad ligament toward the uterine cornu and consistently give off a branch to the ovary on its lateral border. In addition, further vessels were noted to run laterally from the uterine cornu along the ovarian ligament to the medial aspect of the ovary. PI and O(2)Sat measurements imply that the uterine and ovarian vessels contribute almost equally to uterine perfusion. Clinical application by selective ligation of the pelvic vasculature has been utilized in certain gynecological procedures often prone to torrential life-threatening uterine hemorrhage. Selective temporary ligation of the uterine and ovarian vessels has proven useful in the surgical management of chemoresistant gestational trophoblastic disease, in the Strassman procedure, fertility-sparing surgery in ruptured cornual ectopic pregnancies, and unrelenting postpartum hemorrhage. Of the six supplying vessels (ovarian, uterine, and vaginal) to the uterus only two (ovarian or uterine or a combination thereof) are required for uterine viability.     

The interaction of von Willebrand factor-A1 domain with collagen: mutation G1324S (type 2M von Willebrand disease) impairs the conformational change in A1 domain induced by collagen

BACKGROUND: It is established that the A3 domain in von Willebrand factor (VWF) contains the major collagen-binding site. However, there are conflicting reports describing the capacity of the A1 domain to interact with collagen types I and III. METHODS: In this study, we have used recombinant VWF-A1 polypeptides, as well as conformation-specific monoclonal antibodies (mAb), to analyze the A1-collagen interaction. RESULTS: The A1 domain bound to collagen with K(d) approximately 8.0 nm and this binding was blocked by the mAb 6G1, which blocks the interaction between ristocetin and VWF. In addition, collagen-bound A1 protein was able to support flow-dependent adhesion of platelets, demonstrating that the binding sites for collagen and glycoprotein (GP)Ib are different. Analysis with two conformation-specific mAb demonstrated that the structure of the A1 domain changed as a result of the binding to collagen. In contrast, the antibodies failed to detect conformational change in the G1324S mutant (type 2M von Willebrand disease). Thus, direct binding to collagen induces a change in the structural conformation within the VWF-A1 domain, and the G1324S substitution prevents this conformational change. CONCLUSION: This study has shown that the isolated A1 domain can simultaneously bind to collagen and platelet GPIb, supporting platelet adhesion under high-flow conditions. In addition, this study has used mAb to demonstrate that the binding of the isolated A1 domain or full-length VWF to collagen is accompanied by a conformational change in A1 domain.     

急性冠脉综合征患者外周血白细胞表面粘附分子的表达

目的　研究急性冠脉综合征患者外周血中性粒细胞和单核细胞表面粘附分子CD11b、CD18的表达。方法　选择 5 4例急性冠脉综合征患者 ,其中 2 5例为急性心肌梗死患者 ,2 9例为不稳定心绞痛患者。根据疼痛的严重程度将不稳定心绞痛患者按Braunwald分级分为三组 :第一组 (9例 ) ,BraunwaldⅠ级 ;第二组 (8例 )BraunwaldⅡ级 ;第三组 (12例 )BraunwaldⅢ级。选择 12例健康人为正常对照组。采用流式细胞术分析外周血中性粒细胞和单核细胞表面CD11b、CD18的表达。结果　急性冠脉综合征患者外周血中性粒细胞和单核细胞表面CD11b、CD18的表达较正常对照组显著升高 (P <0 .0 0 1) ;不稳定心绞痛患者由第一组到第三组外周血中性粒细胞和单核细胞表面CD11b、CD18的表达是逐渐升高的 ,其中第三组较第一组明显升高 (P <0 .0 5 )。结论　冠心病患者外周血白细胞是激活的 ;随着不稳定心绞痛病情的加重 ,外周血白细胞活性也是增加的 ,白细胞活性状态可能提示了病变斑块存在着炎症反应。     

Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-induced asthma

BACKGROUND: Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) are thought to contribute to the airway inflammation and airway hyper-responsiveness (AHR) of allergic asthma. Some differences from allergic asthma have been noted, including airway neutrophilia, and the involvement of ICAM-1 in toluene diisocyanate (TDI) asthma is currently unclear. OBJECTIVE: We utilized mice lacking ICAM-1 expression (ICAM-1(-/-)) to investigate the role of ICAM-1 in airway inflammation and AHR in TDI-induced asthma. METHODS: Male C57BL/6J mice (ICAM-1(+/+)) and ICAM-1(-/-) mice were intranasally sensitized to TDI solution or solvent alone. Airway inflammation, AHR and cytokine secretion were assessed 24 h after challenge by TDI or solvent. The production of antigen-specific IgG and IgE by TDI sensitized and non-sensitized mice was determined. RESULTS: TDI challenge to ICAM-1(+/+) mice induced an increase in airway inflammatory cell numbers, AHR and cytokine secretion of TNF-alpha, macrophage inflammatory protein-2 (MIP-2), IL-4, IL-5 and IFN-gamma into the bronchoalveolar lavage fluid. All these pathophysiological changes were reduced in ICAM-1(-/-) mice. Serum levels of TDI-specific IgG and IgE of ICAM-1(-/-) and ICAM-1(+/+) mice were comparable. CONCLUSION: These results suggest that ICAM-1 plays an essential role in airway inflammation and AHR in TDI-induced asthma.     

丹参对脑缺血再灌注区白细胞与内皮细胞粘附的影响

目的:研究丹参对脑缺血再灌注损伤后局灶区白细胞与内皮细胞粘附性变化及影响;方法:通过免疫荧光标记技术和显微超高速系统观察脑缺血再灌注及应用丹参后局灶白细胞粘附性的变化。结果:试验表明脑缺血再灌注损伤局部灶区微动脉白细胞附壁指数升高,白细胞与内皮细胞间断裂应力降低,粘附性显著下降。结论:研究结果表明,丹参可显著减轻脑缺血再灌注损伤后内皮细胞的粘附。     

Histamine differentially interacts with tumor necrosis factor-α and thrombin in endothelial tissue factor induction: the role of c-Jun NH2-terminal kinase

BACKGROUND: Histamine plays an important role in vascular disease. Tissue factor (TF) expression is induced in vascular inflammation and acute coronary syndromes. OBJECTIVES: This study examined the effect of histamine on tumor necrosis factor-alpha- (TNF-alpha-) vs. thrombin-induced endothelial TF expression. METHODS AND RESULTS: Histamine (10(-8)-10(-5) mol L-1), TNF-alpha (5 ng mL-1), and thrombin (1 U mL-1) induced TF expression in human endothelial cells. Although TF expression by TNF-alpha and thrombin was identical, histamine augmented TNF-alpha-induced expression 7.0-fold, but thrombin-induced expression only 2.6-fold. Similar responses occurred with TF activity. The H1-receptor antagonist mepyramine abrogated these effects. Differential augmentation by histamine was also observed at the mRNA level. Histamine-induced p38 activation preceded a weak second activation to both TNF-alpha and thrombin. Histamine-induced c-Jun NH2-terminal kinase (JNK) activation was followed by a strong second activation to TNF-alpha, and less to thrombin. Selective inhibition of this second JNK activation by SP600125 reduced TF induction to histamine plus TNF-alpha by 67%, but to histamine plus thrombin by only 32%. Histamine augmented TNF-alpha- and thrombin-induced vascular cell adhesion molecule 1 (VCAM-1) expression to a similar extent. Consistent with this observation, VCAM-1 induction to TNF-alpha and thrombin was mediated by p38, but not by JNK. CONCLUSIONS: Histamine differentially augments TNF-alpha- vs. thrombin-induced TF expression and activity, which is mediated by the H1-receptor, occurs at the mRNA level, and is related to differential JNK activation.     

水蛭注射液对大白鼠血小板粘附和血小板聚集功能的影响

目的　探讨水蛭注射液对大白鼠血小板粘附性和聚集性的影响。方法　采用大白鼠 2 4只 ,随机分成两组 ,实验组给药 ,对照组以实验组同样的方法和剂量给予生理盐水 ,5d后由颈总动脉取血 ,做血小板粘附性和聚集性试验。结果　水蛭注射液对大鼠血小板粘附性和聚集性具有显著的抑制作用 ,实验组与对照组抑制率有显著的统计学意义 (P <0 0 0 1)。结论　水蛭注射液能够抑制大白鼠血小板的粘附和聚集。     

32例腹部开放性损伤的救治体会

目的:探讨开放性腹部损伤的治疗方法。方法:回顾性分析1991年-1994年32例开放性腹部损伤患者的临床资料。结果:开腹探查26例,单纯缝合6例,阴性探查3例,二次手术2例,术后切口感染2例,感染性休克死亡1例,治愈31例,病死率为3.12%。结论:开放性腹部外伤,首先要根据临床表现及辅助检查判定内脏是否损伤,手术时机的掌握是治疗的关键。