Inflammation induced by Bothrops asper venom: release of proinflammatory cytokines and eicosanoids, and role of adhesion molecules in leukocyte infiltration.

Bothrops asper venom (BaV) causes systemic and local effects characterized by an acute inflammatory reaction with accumulation of leukocytes and release of endogenous mediators. In this study, the effects of BaV on the release of the cytokines IL-1, IL-6 and TNF-alpha and the eicosanoids LTB4 and TXA2 in the peritoneal cavity of mice were analyzed. We also investigated the participation of beta2 integrin chain, l-selectin, LFA-1, ICAM-1 and PECAM-1 adhesion molecules in the BaV-induced leukocyte accumulation. Levels of proinflammatory cytokines IL-6 and TNF-alpha, as well as eicosanoids LTB4 and TXA2 were significantly increased after BaV injection (250 microg/kg), whereas no increment in IL-1 was observed. Anti-mouse l-selectin, LFA-1, ICAM-1, PECAM-1 and beta2 integrin chain monoclonal antibodies resulted in a reduction of neutrophil accumulation induced by BaV injection compared with isotype-matched control injected animals. These data suggest that BaV is able to induce the activation of leukocytes and endothelium to express adhesion molecules involved in the recruitment of neutrophils into the inflammed site. Furthermore, these results showed that BaV induces the release of cytokines and eicosanoids in the local of the venom injection; these inflammatory mediators may be important for the initiation and amplification of the inflammatory reaction characteristic from Bothrops sp envenomation.     

养阴清热煎剂对系统性红斑狼疮患者黏附分子表达及狼疮损伤指数的影响

目的:研究中医药对系统性红斑狼疮(SLE)的治疗作用机制及其对SLE器官损害的远期疗效.方法:1999～2003年住院及门诊的SLE患者51例,随机分为以中药养阴清热煎剂为主的中西医结合治疗组(简称治疗组)和单纯西药治疗的对照组(简称对照组),进行了治疗前后血清细胞黏附分子1(ICAM-1)、黏附分子3(ICAM-3)、P-选择素以及SLE损伤指数(SLICC/ACRDI)的研究.结果:SLE患者的ICAM-1、ICAM-3、P-选择素均较正常人明显增高;治疗组治疗后ICAM-1、P-选择素比对照组明显下降;而SLE损伤指数积分显示,治疗组比较稳定,对照组较治疗前有明显增加.结论:提示以中药养阴清热煎剂为主的治疗组对SLE患者的血清黏附分子高表达有明显的抑制作用,并对SLE的器官损害有明显的保护与修复作用.     

针刺对重度颅脑损伤患者脑脊液中IL-8、sICAM-1含量的影响

目的:观察针刺对重度颅脑损伤患者脑脊液中白细胞介素-8(IL-8)、可溶性细胞黏附分子-1(sICAM-1)含量的影响,并探讨针刺治疗的脑保护作用机理.方法:将50例重度颅脑损伤患者随机分为对照组24例和治疗组26例.对照组应用西医常规治疗,治疗组在常规治疗基础上加针刺涌泉和厉兑穴.采用酶联免疫吸附方法(ELISA)检测患者伤后1、2、3、5、7 d脑脊液中IL-8、sI-CAM-1含量.结果:①对照组脑脊液中IL-8、sICAM-1含量在伤后1 d升高,2 d达高峰,3 d开始下降,5 d进一步下降,7 d下降到正常水平;②治疗组脑脊液中IL-8、sICAM-1含量在伤后1 d升高,2 d下降,3 d继续下降,5 d下降到正常水平;③治疗组伤后2、3、5 d脑脊液中IL-8、sICAM-1含量均低于对照组(P＜0.05).结论:针刺能减轻重度颅脑损伤后脑内炎症反应,从而减轻因炎症反应引起的继发性脑损害.     

Purmorphamine increased adhesion,proliferation and expression of osteoblast phenotype markers of human dental pulp stem cells cultured on beta-tricalcium phosphate

ObjectivesGrowth factors play a significant role in cell proliferation and differentiation during different stages of the bone repair. However, several limitations have been brought researchers attention to an osteoinductive small molecule including Purmorphamine. In this study, we aimed to evaluate the effect of Purmorphamine on adhesion, proliferation and differentiation of human dental pulp stem cells (hDPSCs) seaded on beta-tricalcium phosphate (β-TCP) granules.MethodshDPSCs were established from extracted wisdom teeth of healthy volenteers. Cells at passage 3 were seeded on β-TCP in the presence or absence of Purmorphamine. Cell adhesion and proliferation were assessed using scanning electeron microscopy (SEM) and DNA counting assay, respectively, after 1, 3 and 5 days. Then, hDPSCs seeded on β-TCP were subjected to osteogenic medium with or without Purmorphamine. After 7 and 14 days osteogenic diffrentiation capability of hDPSCs were determined using real-time RT-PCR and alkaline phosphatase (ALP) activity assay.ResultsThe significant increase in amount of DNA was observed at day 3 and 5 in the presence of Purmorphamine. SEM imaging also was confirmed the DNA counting assay; in all given time points, hDPSC attachment and growth was significantly higher in the presence of Purmorphamine. ALP activity was increased by Purmorphamine at both 7 and 14 days of induction. Purmorphamine showed to effect on osteopontin expression at earlier stage of osteogenic differentiation, whereas for osteocalcin expression, this effect was more evident at later stage of differentiation.ConclusionPurmorphamine had a promotive effect on adhesion, proliferation and osteogenic differentiation of hDPSCs cultured on β-TCP. The outcome of the current study would help in development of in vitro culture conditions for better osteogenic differentiation of hDPSCs prior to transplantation.     

Soluble Adhesion Molecules and Cytokines in Tumor-associated Tissue Eosinophilia of Nasopharyngeal Carcinoma

The phenomenon of tumor-associated tissue eosinophilia (TATE) is seen in some cases of nasopharyngeal carcinoma (NPC) and is characterized by the eosinophils breaking through the vascular wall and pervading the tumor stroma. The margination and trans-endothelial migration of eosinophils in a typical inflammatory reaction depend on the activating effects of certain cytokines and the expression of adhesion molecules on the eosinophils and endothelial cells. In order to investigate whether the adhesion molecules and activating cytokines play a role in eosinophil tumor infiltration, we measured the serum levels of 3 adhesion molecules, intercellular adhesion molecule-1, E-selectin and vascular cell adhesion molecule-1, and 2 cytokines, IL-3 and IL-5, in 60 NPC patients and 40 normal healthy subjects. We found that the NPC patients had higher serum levels of all three soluble adhesion molecules than the normal subjects but the levels of adhesion molecules failed to correlate with the TATE phenomenon. The levels of IL-3 and IL-5 appeared not to differ between the NPC and control groups. We postulate that the three soluble adhesion molecules do not play a major role in TATE and that their elevation in serum may be due to local and/or systemic immune responses.     

Expression of DNAM-1 (CD226) on inflammatory monocytes

DNAM-1 is an activating receptor expressed on NK cells and T cells and plays an important role in cytotoxicity of these cells against target cells. Although the role of DNAM-1 in the function of T cells and NK cells has been well studied, the expression and function of DNAM-1 on myeloid cells have been incompletely understood. In this study, we investigated expression of DNAM-1 on monocyte subsets in mouse peripheral blood and found that only inflammatory monocytes (iMos), but not patrolling monocytes (pMos), expressed high levels of DNAM-1. In addition, we found that DNAM-1 was highly expressed on iMos, rather than pMos, also in human. Furthermore, we found that DNAM-1 on inflammatory monocytes was involved in cell adhesion to CD155-expressing cells. Therefore, we propose that expression of DNAM-1 on inflammatory monocytes are evolutionally conserved and act as an adhesion molecule on blood inflammatory monocytes.     

Soluble Adhesion Molecules in Coronary Surgery and Cardiopulmonary Bypass with Pump Prime Aprotinin

Objective : The purpose of the present study was to establish whether pump prime aprotinin could influence soluble adhesion molecules in patients undergoing elective coronary artery bypass surgery. Design : Thirty patients admitted for first-time elective coronary artery bypass surgery were randomized into control or aprotinin groups. Patients in the aprotinin group received 280 mg of aprotinin in the pump prime. Plasma levels of soluble adhesion molecules were analyzed perioperatively. Results : There were no significant changes in plasma sE-selectin after the operation in either group. Plasma sP-selectin increased significantly up to 20 h after reperfusion to the myocardium. Plasma sICAM-1 decreased in the early stage after cardiopulmonary bypass (CPB), then recovered at 4 h after reperfusion and a significant increase in sICAM-1 was observed 20 h later. There were no significant differences between the groups in postoperative changes in sP-selectin ( p = 0.21) and sICAM-1 ( p = 0.91). Conclusion : Pump prime aprotinin did not influence plasma levels of E-selectin, P-selectin and ICAM-1 in the present patients. The present results do not support the concept of an anti-inflammatory effect of pump prime aprotinin.     

Biofilm-formation capability depends on environmental oxygen concentrations in Candida species

BackgroundAlthough oxygen concentrations inside of the human body vary depending on organs or tissues, few reports describe the relationships between biofilm formation of Candida species and oxygen concentrations. In this study, we investigated the biofilm-forming capabilities of Candida species under various oxygen conditions.MethodsWe evaluated the adhesion and biofilm formation of Candida albicans and C. tropicalis under aerobic, microaerobic (oxygen concentration 5%), or anaerobic conditions. We also examined how oxygen concentration affects adhesion/maturation by changing adhesion/maturation phase conditions. We used crystal violet assay to estimate the approximate biofilm size, performed microscopic observation of biofilm morphology, and evaluated adhesion-associated gene expression.ResultsThe adhered amount was relatively small except for a clinical strain of C. tropicalis. Our biofilm-formation analysis showed that C. albicans formed a higher-size biofilm under aerobic conditions, while C. tropicalis favored microaerobic conditions to form mature biofilms. Our microscopic observations were consistent with these biofilm-formation analysis results. In particular, C. tropicalis exhibited more hyphal formation under microaerobic conditions. By changing the adhesion/maturation phase conditions, we represented that C. albicans had favorable biofilm-formation capability under aerobic conditions, while C. tropicalis showed enhanced biofilm formation under microaerobic adhesion conditions. In good agreement with these results, the C. tropicalis adhesion-associated gene expression tended to be higher under microaerobic or anaerobic conditions.ConclusionsC. albicans favored aerobic conditions to form biofilms, whereas C. tropicalis showed higher biofilm-formation ability and promoted hyphal growth under microaerobic conditions. These results indicate that favorable oxygen conditions significantly differ for each Candida species.