BACKGROUND & AIMS: OBJECTIVE:To evaluate the predictive value of gestational age and maternal serum β-hCG concentration for the determination of the depth of trophoblastic invasion into the tubal wall. METHODS:This is a retrospective trial conducted on women with a diagnosis of ampullary pregnancy (71) who were submitted to salpingectomy. Serum β-hCG measurements were obtained at the initial admission of hospital. Histological investigation was performed by a single well-experienced pathologist who was blind to the clinical and laboratory characteristics of the patients. Ampullary pregnancy was classified histologically according to the depth of trophoblastic infiltration into tubal wall: trophoblast limited to the tubal mucosa (stage I), extended to muscularis layer (stage II) and complete tubal wall infiltration up to serosal layer (stage III). RESULTS:There was a significant difference in maternal serum β-hCG concentrations regarding the histological stages of trophoblastic invasion. The serum β-hCG concentrations that the best predicted for stage III trophoblastic invasion was 6,475 mIU/ml, with a sensitivity of 100 %, a specificity of 92 %. CONCLUSION:The depth of trophoblastic tissue infiltration into tubal wall is correlated with serum β-hCG levels, but not with gestational age. These findings may explain the reason for conservative management failure of EP in women with high β-hCG concentrations.

背景与目标：

BACKGROUND & AIMS: :In the presence of ascorbate/H(2)O(2), ATP-Fe(2+) or AMP-PNP-Fe(2+) complexes act as affinity cleavage reagents, mediating selective cleavage of the alpha subunit of Na,K-ATPase at high affinity ATP-Mg(2+) sites. The cleavages reveal contact points of Fe(2+) or Mg(2+) ions. In E(1) and E(1)Na conformations, two major cleavages are detected within the conserved (708)TGDGVNDSPALKK sequence (at V712 and nearby), and one (E(1)Na) or two (E(1)) minor cleavages near V440. In media containing sodium and ATP, Fe(2+) substitutes for Mg(2+) in activating phosphorylation and ATP hydrolysis. In the E(1)P conformation, cleavages are the same as in E(1). Fe(2+) is not bound tightly. By contrast, in the E(2)P conformation, the pattern is different. A major cleavage occurs near the conserved sequence (212)TGES, whereas those in TGDGVNDSPALKK are less prominent. Fe(2+) is bound very tightly. On E(2)P hydrolysis, the Fe(2+) dissociates. The results are consistent with E(1)<-->E(2) conformation-dependent movements of cytoplasmic domains and sites for P(i) and Mg(2+) ions, inferred from previous Fe-cleavage experiments. Furthermore, these concepts fit well with the crystal structure of Ca-ATPase [Toyoshima, C., Nakasako, M., Nomura, H. & Ogawa, H. (2000) Nature (London) 405, 647-655]. Altered ligation of Mg(2+) ions in E(2)P may be crucial in facilitating nucleophilic attack of water on the OP bond. Mg(2+) ions may play a similar role in all P-type pumps. As affinity cleavage reagents, ATP-Fe(2+) or other nucleotide-Fe(2+) complexes could be widely used to investigate nucleotide binding proteins.

背景与目标： : 在抗坏血酸盐/H(2)O(2) 存在下，ATP-Fe(2 +) 或AMP-PNP-Fe(2 +) 配合物作为亲和裂解试剂，介导Na的 α 亚基的选择性裂解，高亲和力ATP-Mg(2 +) 位点的K-ATP酶。裂解揭示了Fe(2) 或Mg(2) 离子的接触点。在E(1) 和E(1)Na构象中，在保守 (708)TGDGVNDSPALKK序列 (在V712和附近) 内检测到两个主要切割，以及在v440附近检测到一个 (E(1)Na) 或两个 (E(1)) 次要切割。在含有钠和ATP的介质中，Fe(2) 代替Mg(2) 激活磷酸化和ATP水解。在E(1)P构象中，裂解与E(1) 相同。Fe(2 +) 结合不紧。相比之下，在E(2)P构象中，模式是不同的。在保守序列 (212)TGES附近发生主要切割，而TGDGVNDSPALKK中的切割较不突出。Fe(2 +) 结合得非常紧密。在E(2)P水解时，Fe(2) 解离。结果与E(1)<->E(2) 胞质结构域和P(i) 和Mg(2) 离子位点的构象依赖性运动一致，这是从先前的Fe裂解实验得出的。此外，这些概念与Ca-ATPase的晶体结构非常吻合 [Toyoshima，C.，Nakasako，M.，Nomura，H.和Ogawa，H. (2000) 自然 (伦敦) 405，647-655]。E(2)P中Mg(2) 离子的连接改变对于促进水对OP键的亲核攻击可能至关重要。Mg(2) 离子可能在所有P型泵中起相似的作用。作为亲和裂解试剂，ATP-Fe(2) 或其他核苷酸-Fe(2) 复合物可广泛用于研究核苷酸结合蛋白。

BACKGROUND & AIMS: :CD45 is the most prominent membrane protein on lymphocytes. The function and regulation of this protein tyrosine phosphatase remain largely obscure, mainly because of the lack of a known ligand, and it still remains unknown whether such tyrosine phosphatases are subject to extracellular control at all. We report that an anti-CD45RB antibody (Ab) that prevents rejection and induces tolerance activates CD45RB tyrosine phosphatase enzymatic activity in T lymphocytes, allowing us to directly monitor the effects of increased CD45RB activity on signal transduction. Using both kinase substrate peptide arrays as well as conventional biochemistry, we also provide evidence of the various kinases involved in bringing about the inhibitory effect of this Ab on CD3-induced T-cell receptor signaling. Furthermore, we report that activated CD45RB translocates to lipid rafts and interferes with lipid raft localization and activation state of CD45 substrate Lck. Thus, these findings indeed prove that CD45 is subject to extracellular control and also define a novel mechanism by which receptor tyrosine phosphatases control lymphocyte biology and provide further insight into the intracellular signaling pathways effected by anti-CD45RB monoclonal Ab treatment.

背景与目标： : CD45是淋巴细胞上最突出的膜蛋白。这种蛋白质酪氨酸磷酸酶的功能和调节在很大程度上仍然不清楚，这主要是由于缺乏已知的配体，并且仍然未知这种酪氨酸磷酸酶是否完全受细胞外控制。我们报告了一种防止排斥和诱导耐受性的anti-CD45RB抗体 (Ab) 激活T淋巴细胞中的CD45RB酪氨酸磷酸酶酶活性，使我们能够直接监测CD45RB活性增加对信号转导的影响。使用激酶底物肽阵列以及常规生物化学，我们还提供了涉及这种Ab对CD3-induced T细胞受体信号传导的抑制作用的各种激酶的证据。此外，我们报道活化的CD45RB易位于脂筏，并干扰CD45底物Lck的脂筏定位和激活状态。因此，这些发现确实证明了CD45受细胞外控制，并且还定义了一种新的机制，通过该机制受体酪氨酸磷酸酶控制淋巴细胞生物学，并提供了对anti-CD45RB单克隆Ab治疗所影响的细胞内信号通路的进一步了解。

BACKGROUND & AIMS: :A model of brain ischemia induced by staged ligation of the left and right common carotid arteries has been developed in experiments on rats. The use to this model led to reduction of animal mortality. On days 2-5 after the second ligature, the animals lost weight, the level of their CNS vulnerability increased, the volume of perceived information reduced, adaptation to environmental conditions and reproduction of conditioned reflexes were disordered. Focal and diffuse destructive changes in the nerve and glia cells were found in the cerebral cortex, hippocampus, and thalamic nuclei. The severity of disorders in the blood supply to the brain depended on the interval between ligation of the carotid arteries. This recommends this model for evaluation of the efficiency of drugs of various pharmacological groups.

背景与目标： : 在大鼠实验中，已经开发出由左右颈总动脉分期结扎引起的脑缺血模型。使用此模型可降低动物死亡率。在第二次结扎后的第2-5天，动物体重减轻，中枢神经系统脆弱性增加，感知信息量减少，对环境条件的适应和条件反射的繁殖紊乱。在大脑皮层，海马和丘脑核中发现了神经和神经胶质细胞的局灶性和弥漫性破坏性变化。脑部血液供应障碍的严重程度取决于结扎颈动脉之间的间隔。这建议该模型用于评估各种药理学组的药物的效率。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: BACKGROUND:Angiotensin II (Ang II) promotes atherosclerotic vascular diseases, in which proinflammatory and proliferative effects play a major pathogenic role. Ang II up-regulates chemokines, such as monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha, which are important pro-inflammatory factors mediating infiltration of inflammatory cells into atherosclerotic lesion. The aim of the present study was to determine whether the presence of MCP-1 or MIP-1alpha is essential in Ang II-induced intimal hyperplasia in the carotid artery ligation model. METHODS:Six-month-old male C57BL/6-, MCP-1-, or MIP-1alpha-deficient mice underwent ligation of the common left carotid artery and were randomly assigned to receive either vehicle or Ang II (1.4 mg kg(-1) day(-1)) via a subcutaneously implanted osmotic infusion pump (model 2004, Alzet) for 4 weeks. RESULTS:Ang II not only increased MCP-1 and MIP-1alpha production but also enhanced neo-intimal formation, media thickness, and adventitia development in the ligated carotid arteries in C57BL/6 mice. However, MCP-1 or MIP-1alpha deficiency failed to affect intimal hyperplasia in vascular remodeling. CONCLUSION:These results indicate that MCP-1 or MIP-1alpha may not be essential in mediating the proliferative effects of Ang II, a major pathological changes in intimal hyperplasia in the carotid artery ligation model.

背景与目标：

BACKGROUND & AIMS: :Fifteen patients with laparoscopically diagnosed tubal pregnancy and constant or rising plasma beta-hCG levels were treated with prostaglandin F2 alpha and prostaglandin E2. Prostaglandin F2 alpha (5 mgms diluted in 10 cc of isotonic sodium solution) was injected transabdominally with a 22 gauge spinal needle during laparoscopy into the Fallopian tube. Prostaglandin E2 (500 micrograms ms) was given intramuscularly during three consecutive postoperative days. The treatment was defined as successful if plasma beta-hCG levels declined below the lower limit of detection and no further intervention other than prostaglandin application was required. The treatment was successful in eight patients. Six patients underwent laparotomy and salpingotomy because of rising beta-hCG levels. None of the treated patients displayed any adverse reactions following prostaglandin F2 alpha application. One patient underwent explorative laparotomy during the second postoperative day because of lower abdominal pain. During operation, no pathological change could be found. This patient was excluded from the study. In the group treated successfully (n = 8) seven out of eight patients had beta-hCG levels below 2500 mlU/ml preoperatively. In the unsuccessfully treated group (n = 6), four out of six patients had beta-hCG levels above 2500 mlU/ml preoperatively. Mean duration of beta-hCG decline to 10 percent of the maximum preoperative value was 15.8 +/- 8.64 days (mean +/- S.D.). Postoperatively, hysterosalpingography was performed in six out of eight successfully treated patients after three menstrual cycles (one patient had an intrauterine pregnancy, one patient refused written consent). The Fallopian tubes were patent bilaterally in all six patients.

背景与目标： : 用前列腺素f2α 和前列腺素e2治疗15例经腹腔镜诊断为输卵管妊娠且血浆 β-hCG水平持续或升高的患者。在腹腔镜检查期间，将前列腺素f2α (在10 cc的等渗钠溶液中稀释的5 mgms) 用22号脊柱针经腹注射到输卵管中。在术后连续三天肌肉注射前列腺素E2 (500微克ms)。如果血浆 β-hCG水平下降到检测下限以下，并且除前列腺素应用外不需要进一步干预，则治疗被定义为成功。八名患者的治疗成功。由于 β-hCG水平升高，六名患者接受了剖腹手术和输卵管切开术。在应用前列腺素f2α 后，治疗的患者均未显示任何不良反应。由于腹痛较低，一名患者在术后第二天接受了探索性剖腹手术。术中未见病理改变。该患者被排除在研究之外。在成功治疗的组中 (n = 8)，八名患者中有七名术前 β-hCG水平低于2500 mlU/ml。在未成功治疗组 (n = 6) 中，六名患者中有四名术前 β-hCG水平高于2500 mlU/ml。Β-hCG下降至最大术前值10% 的平均持续时间为15.8 +/- 8.64天 (平均值 +/-s.d.)。术后，在三个月经周期后，八名成功治疗的患者中有六名进行了子宫输卵管造影 (一名患者宫内妊娠，一名患者拒绝书面同意)。所有六名患者的输卵管均双侧未闭。

BACKGROUND & AIMS: OBJECTIVE:To determine the impact of oil-based versus water-based contrast on pregnancy and live birth rates ≤5 years after hysterosalpingography (HSG) in infertile women. DESIGN:A 5-year follow-up study of a multicenter randomized trial. SETTING:Hospitals. PATIENT(S):Infertile women with an ovulatory cycle, 18-39 years of age, and having a low risk of tubal pathology. INTERVENTION(S):Use of oil-based versus water-based contrast during HSG. MAIN OUTCOME MEASURE(S):Ongoing pregnancy, live births, time to ongoing pregnancy, second ongoing pregnancy. RESULT(S):A total of 1,119 women were randomly assigned to HSG with oil-based contrast (n = 557) or water-based contrast (n = 562). After 5 years, 444 of 555 women in the oil group (80.0%) and 419 of 559 women in the water group (75.0%) had an ongoing pregnancy (relative risk [RR] 1.07; 95% confidence interval [CI] 1.00-1.14), and 415 of 555 women in the oil group (74.8%) and 376 of 559 women in the water group (67.3%) had live births (RR 1.11; 95% CI 1.03-1.20). In the oil group, 228 pregnancies (41.1%) were conceived naturally versus 194 (34.7%) pregnancies in the water group (RR 1.18; 95% CI 1.02-1.38). The time to ongoing pregnancy was significantly shorter in the oil group versus the water group (10.0 vs. 13.7 months; hazard ratio, 1.25; 95% CI 1.09-1.43). No difference was found in the occurrence of a second ongoing pregnancy. CONCLUSION(S):During a 5-year time frame, ongoing pregnancy and live birth rates are higher after tubal flushing with oil-based contrast during HSG compared with water-based contrast. More pregnancies are naturally conceived and time to ongoing pregnancy is shorter after HSG with oil-based contrast. CLINICAL TRIAL REGISTRATION NUMBER:Netherlands Trial Register (NTR) 3270 and NTR6577(www.trialregister.nl).

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:We sought to clarify possible pathological conditions of the bony portion of the eustachian tube (ET) in patients with ET stenosis. METHODS:We measured the total length, the cross-sectional area of the bony frame, and the air space of the ET lumen at an interval of 1 mm on the reconstructed computed tomographic images of the ET using a multiplanar reconstruction method on 20 normal subjects (control group) and 25 patients with stenotic ET judged by the inflation test (stenotic group). RESULTS:In the cross-sectional areas, both the bony frame and air space were significantly smaller in the stenotic group than in the control group. The soft tissue ratio was significantly greater in most parts of the mid-bony portion and the tympanic orifice of the stenotic group than in those of the control group. At the anterior tip of the bony portion, only the bony frame was found to be significantly smaller in the stenotic group than in the control group. CONCLUSIONS:We suggest that a smaller framework of the bony ET may possibly be related to the pathogenesis of ET stenosis.

背景与目标：

BACKGROUND & AIMS: :[This corrects the article DOI: 10.1186/s13039-014-0096-1.].

背景与目标： : [这更正了文章DOI: 10.1186/s13039-014-0096-1。]。

BACKGROUND & AIMS: Outpatient surgery benefits patients only if postoperative sequelae are effectively treated. After laparoscopic tubal ligation (TL) intense pain and consequent postoperative nausea and vomiting (PONV) has been a problem delaying recovery and resulting in hospital admission. Ninety patients were randomised to this double-blind study, the aim being to evaluate the effect of balanced analgesia on postoperative pain and recovery after sterilization. The balanced analgesia group received 5 ml of 2% lidocaine gel on the sterilization clips and perioperatively 200 mg of ketoprofen i.v. The lidocaine group received 5 ml of 2% lidocaine gel on the clips and placebo i.v. perioperatively. The placebo group received 5 ml of placebo gel on the clips and placebo i.v. perioperatively. Infusion of propofol and 67% nitrous oxide in oxygen were used for maintenance of anesthesia. Succinylcholine and vecuronium were used for muscle relaxation and 0.1 mg of fentanyl i.v. was given to all patients at induction of anesthesia. Postoperative pain and analgesic requirements, incidence of PONV and need for antiemetic medication were all significantly lower in the balanced analgesia group. Home readiness was consistently achieved 70-90 min sooner in the balanced analgesia group compared to the other groups (P < 0.01 between the balanced analgesia and the placebo group), and the patients were able to return to normal activity sooner (cumulatively 93% of the patients in the balanced analgesia group vs. 60% in the other two groups (P < 0.01 between the balanced analgesia and the other groups) had returned to normal activity on the 2nd postoperative day). It is concluded that in patients undergoing laparoscopic TL the combination of analgesic regimens with different mechanisms of action offer a simple and efficient way of postoperative pain relief, as well as an improvement of quality (i.e. less PONV) and speed of recovery.

背景与目标： 只有有效治疗术后后遗症，门诊手术才能使患者受益。腹腔镜输卵管结扎术 (TL) 后，剧烈的疼痛和随之而来的术后恶心和呕吐 (PONV) 一直是延迟康复并导致住院的问题。90名患者被随机纳入这项双盲研究，目的是评估平衡镇痛对术后疼痛和绝育后恢复的影响。平衡镇痛组在灭菌夹上5毫升2% 利多卡因凝胶，并在围手术期200 mg酮洛芬静脉注射。利多卡因组在围手术期接受2% 利多卡因凝胶5毫升和安慰剂。安慰剂组接受5毫升在夹子上的安慰剂凝胶和安慰剂i.v.围手术期。在氧气中输注丙泊酚和67% 一氧化二氮用于维持麻醉。琥珀胆碱和维库溴铵用于肌肉松弛和0.1 mg芬太尼静脉注射。在麻醉诱导时给予所有患者。平衡镇痛组的术后疼痛和镇痛需求，PONV发生率和止吐药物需求均显着降低。与其他组相比，平衡镇痛组始终提前70-90分钟达到家庭准备 (平衡镇痛组和安慰剂组之间的P <0.01)，并且患者能够更快地恢复正常活动 (平衡镇痛组与其他两组的60% 患者在术后第2天已恢复正常活动，累积93% (平衡镇痛与其他组之间的0.01 P

BACKGROUND & AIMS: :CD40 is expressed in normal human keratinocytes, especially in the basal cell layer. We have recently reported that CD40 ligation strongly inhibits keratinocyte proliferation and induces their differentiation. In this study, the CD40 pathway that prevents keratinocyte growth was investigated. We first reported that interferon-gamma treatment potentiated the CD40-mediated inhibition of keratinocyte proliferation. CD40-CD40 ligand interactions, in the presence or absence of interferon-gamma, neither enhanced spontaneous keratinocyte apoptosis, nor did it enhance apoptosis induced by various agents. More importantly, we showed that CD40 signaling altered the keratinocyte cell cycle, as demonstrated by a decreasing number of cells in the G1 and S phases and an accumulation in G2/M phase of the cell cycle. Furthermore, western blot analysis of cell cycle regulatory proteins, showed a decrease in cyclin A and E expression in CD40-activated keratinocytes. Collectively, these results indicate that CD40 ligation inhibits keratinocyte renewal by a mechanism independent of cell apoptosis and that modulation of the keratinocyte cell cycle is an additional outcome of CD40 signaling.

背景与目标： : CD40在正常人角质形成细胞中表达，特别是在基底细胞层中表达。我们最近报道CD40连接强烈抑制角质形成细胞增殖并诱导其分化。在这项研究中，研究了防止角质形成细胞生长的CD40途径。我们首先报道了干扰素-γ 治疗增强了角质形成细胞增殖的CD40-mediated抑制作用。在存在或不存在干扰素-γ 的情况下，CD40-CD40配体相互作用既不会增强自发性角质形成细胞的凋亡，也不会增强由各种药物诱导的凋亡。更重要的是，我们显示CD40信号传导改变了角质形成细胞的细胞周期，这通过在G1和S期的细胞数量减少以及在细胞周期的G2/M期的积累来证明。此外，细胞周期调节蛋白的western印迹分析显示CD40-activated角质形成细胞中细胞周期蛋白a和E表达降低。总的来说，这些结果表明CD40连接通过独立于细胞凋亡的机制抑制角质形成细胞的更新，而角质形成细胞周期的调节是CD40信号传导的另一结果。

BACKGROUND & AIMS: We have reviewed and summarized 12 years of experience in treating hemorrhoids, a condition that affects 4.4% of the Western population, of whom a third are symptomatic and need treatment. During this time, in a proctological outpatient clinic of an urban hospital, 2,934 patients with second- and third-degree hemorrhoids were treated by rubber band ligation (RBL), usually one ligation per session. Of these patients, 79% were completely cured, 18% needed one or more additional sessions of treatment, and 2.1% failed to be cured by RBL and were referred for conventional hemorrhoidectomy. We found that by using this safe and convenient treatment we can save hundreds of hospitalization days and thousands of sick-leave days per year.

背景与目标： 我们回顾并总结了治疗痔疮的12年经验，痔疮是一种影响4.4% 西方人群的疾病，其中三分之一是有症状的，需要治疗。在此期间，在城市医院的直肠门诊诊所中，通过橡皮筋结扎 (RBL) 治疗了2,934名二度和三度痔疮患者，通常每次结扎一次。在这些患者中，79% 例完全治愈，18% 例需要一次或多次额外治疗，2.1% 例未能通过RBL治愈，并被转诊为常规痔疮切除术。我们发现，通过使用这种安全便捷的治疗方法，我们每年可以节省数百个住院日和数千个病假日。

BACKGROUND & AIMS: INTRODUCTION:Tubal rupture seems to be linked to a disturbance in maternal immune response and trophoblast cell invasion. The immunomodulating activity of endometrial cells is necessary for the coexistence of activated immune cells and endometrial cells. RCAS1 and metallothionein (MT) participate in this process. MATERIAL AND METHODS:Tissue samples derived from fallopian tubes and endometrium were collected during one surgical procedure and divided into three groups: unruptured ectopic pregnancy (EP) without bleeding, unruptured EP with hemorrhage into the peritoneal cavity, and ruptured tubal pregnancy. Immunoreactivity of MT, RCAS1, CD56, CD3, CD69 and CD25 were assessed by immunohistochemical methods. RESULTS:The number of CD3+ and CD56+ cells as well as CD69 antigen immunoreactivity in ruptured tubal mucosa of EP were statistically significantly higher than those measured for unruptured EP without bleeding, while at the same time the number of CD56+ cells in endometrium was statistically significantly lower. The growth of immune cell numbers in tubal mucosa during tubal rupture was not associated with an adequate MT and RCAS1 level. CONCLUSION:Tubal perforation seems to be linked to a concentration of immune cells and a growth of their activity without an adequate increase of the level of proteins compensating for immune cell response.

背景与目标：

BACKGROUND & AIMS: :Sepsis is a systemic inflammatory response resulting from local infection due, at least in part, to impaired neutrophil migration. IL-12 and IL-18 play an important role in neutrophil migration. We have investigated the mechanism and relative role of IL-12 and IL-18 in polymicrobial sepsis induced by cecal ligation and puncture (CLP) in mice. Wild-type (WT) and IL-18(-/-) mice were resistant to sublethal CLP (SL-CLP) sepsis. In contrast, IL-12(-/-) mice were susceptible to SL-CLP sepsis with high bacteria load in peritoneal cavity and systemic inflammation (serum TNF-alpha and lung neutrophil infiltration). The magnitude of these events was similar to those observed in WT mice with lethal CLP sepsis. The inability of IL-12(-/-) mice to restrict the infection was not due to impairment of neutrophil migration, but correlated with decrease of phagocytosis, NO production, and microbicidal activities of their neutrophils, and with reduction of systemic IFN-gamma synthesis. Consistent with this observation, IFN-gamma(-/-) mice were as susceptible to SL-CLP as IL-12(-/-) mice. Moreover, addition of IFN-gamma to cultures of neutrophils from IL-12(-/-) mice restored their phagocytic, microbicidal activities and NO production. Mortality of IL-12(-/-) mice to SL-CLP was prevented by treatment with IFN-gamma. Thus we show that IL-12, but not IL-18, is critical to an efficient host defense in polymicrobial sepsis. IL-12 acts through induction of IFN-gamma and stimulation of phagocytic and microbicidal activities of neutrophils, rather than neutrophil migration per se. Our data therefore provide further insight into the defense mechanism against this critical area of infectious disease.

背景与目标： 败血症是由局部感染引起的全身性炎症反应，至少部分原因是中性粒细胞迁移受损。IL-12和IL-18在中性粒细胞迁移中起重要作用。我们已经研究了IL-12和IL-18在盲肠结扎和穿刺 (CLP) 诱导的小鼠微生物败血症中的作用和相关作用。野生型 (WT) 和IL-18(-/-) 小鼠对亚致死性CLP (sl-clp) 败血症具有抗性。相反，IL-12(-/-) 小鼠对sl-clp败血症易感，腹膜腔细菌负荷高，全身炎症 (血清TNF-α 和肺中性粒细胞浸润)。这些事件的程度与在致命CLP败血症的WT小鼠中观察到的相似。IL-12(-/-) 小鼠无法限制感染不是由于嗜中性粒细胞迁移受损，而是与嗜中性粒细胞的吞噬作用，NO产生和杀微生物活性降低以及全身性IFN-γ 合成减少有关。与该观察结果一致，IFN-γ (-/-) 小鼠与IL-12(-/-) 小鼠一样易受sl-clp影响。此外，向来自IL-12(-/-) 小鼠的中性粒细胞培养物中添加IFN-γ 恢复了其吞噬，杀微生物活性和NO产生。IL-12(-/-) 小鼠对sl-clp的死亡率通过IFN-γ 处理来预防。因此，我们表明，IL-12而非IL-18对于微生物败血症的有效宿主防御至关重要。IL-12通过诱导IFN-γ 和刺激中性粒细胞的吞噬和杀微生物活性而起作用，而不是中性粒细胞本身的迁移。因此，我们的数据提供了针对这一关键传染病领域的防御机制的进一步见解。