单核巨噬细胞对HSV－1的抵抗及LPS、BCG对其的影响

以ＨＳＶ－１接种人单核细胞系Ｕ９３７和小鼠腹腔巨噬细胞，通过病毒感染滴度测定，间接荧光抗体试验检测病毒抗原及多聚酶链反应检测病毒基因，在体外实验中研究了单核巨噬细胞对ＨＳＶ－１的抗性及其影响因素。结果证实，Ｕ９３７和小鼠腹腔巨噬细胞均能逐步清除ＨＳＶ－１，从感染中恢复；１０～２０μｇ／ｍｌＬＰＳ处理细胞能削弱细胞的抗性、促进病毒基因表达，而５μｇ／ｍｌＢＣＧ能增强细胞的抗性、加速病毒的灭活和清除。     

The effect of chronic otitis media on the immunoreactivity of human inner ear

Twenty temporal bones (TBs) were removed from autopsy cases and prepared for immunohistochemical examination. Ten TBs were free of ear disease whereas the other ten TBs showed the signs of chronic otitis media. Expression of markers for monocyte-macrophages¶(25F9, 27E10) and natural killer cells (anti-Leu-11) was examined immunohistochemically. There were no specific positive stainings with 25F9 or anti-Leu-11 antibodies in any of the specimens. Staining for 27E10 was found to be negative in each section obtained from normal cochlea. However, 27E10 positivity was detected in three of ten TBs with signs of chronic ear inflammation. This positivity can be explained by two theories: (1) activated monocytes can enter the inner ear from the systemic circulation as a consequence of chronic antigen challenge; (2) mesothelial cells could become activated as a result of a cross-reaction, with resultant positivity. Development of sensorineural hearing loss in some cases of chronic otitis media may be due to these immunological reactions.     

Characterization of Monocyte-Macrophage-Lineage Cells Induced from CD34<Superscript>+</Superscript> Bone Marrow Cells In Vitro

We characterized the expression of cell surface antigens and cytokine-secreting ability of monocyte-macrophage-lineage cells induced in vitro from CD34+ bone marrow cells. After cultivation for 3 weeks, we observed 2 distinct cell fractions: a floating small, round cell fraction and an adherent large, protruding cell fraction. Both cell fractions expressed myelocyte-monocyte-lineage antigens, but mature-macrophage markers such as CD206 were expressed only by the adherent cells. An assessment of cells cultured for 5 weeks revealed spontaneous secretion of interleukin 8 (IL-8) and IL-6, and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) secretion in both fractions, but only the adherent cell fraction secreted IL-10 after LPS stimulation. In contrast, both fractions of cells cultured for 3 weeks spontaneously secreted low levels of IL-8, but none of the other cytokines. Upon LPS stimulation, the cells secreted IL-6 and TNF-alpha, but not IL-10. We also assessed the effect of granulocyte colony-stimulating factor (G-CSF) pretreatment on TNF-alpha secretion by each cell fraction and found that G-CSF reduced TNF-alpha secretion only in the adherent fraction of cells cultured for 3 weeks. Monocyte-macrophage-lineage cells induced in vitro should provide an ideal model for functional analysis of monocyte-macrophage cells.     

紫草素对大鼠佐剂性关节炎滑膜炎症的影响

目的：探讨紫草素对佐剂性关节炎大鼠滑膜炎症的影响。方法：SD大鼠分为4组（每组10只）：正常对照组,佐剂性关节炎组,甲氨蝶呤治疗组,紫草素治疗组。测量大鼠后肢关节肿胀程度,实验第二十一天杀死大鼠,分离右后肢关节滑膜,应用免疫组织化学方法结合病理学图像分析系统,研究滑膜组织中单核-巨噬细胞（CCR5阳性）的浸润情况。结果：甲氨蝶呤和紫草素均能减轻关节肿胀（P〈0.05）。甲氨蝶呤治疗组和紫草素治疗组关节滑膜CCR5阳性细胞明显减少,且紫草素治疗组更低。结论：紫草素减轻大鼠佐剂性关节炎的炎症反应,减轻关节肿胀和减少滑膜组织炎症细胞浸润,为紫草素治疗类风湿关节炎（RA）提供了实验依据。     

Potential Value of Cetylmannoside-modified Liposomes as Carriers of Macrophage Activators to Human Blood Monocytes

The present study was undertaken to examine the potential value of cetylmannoside-modified multilamellar liposomes (Man-MLV) as carriers for transfer of macrophage activators to blood monocytes. Highly purified blood monocytes were isolated by centrifugal elutriation from healthy donors under cndotox in-free conditions. Freshly prepared monocytes phagocytosed Man-MLV to a lesser extent than monocyte-derived macrophages, but they took up Man-MLV much more effectively than control liposomes without cetylmannoside (control MLV). Phagocytosis of Man-MLV, but not control MLV by monocytes was inhibited by addition of D-mannose, but not of D-galactose. Desmethyl-muramyl dipeptide (norMDP) entrapped in Man-MLV was far more effective than norMDP entrapped in MLV in activating monocytes to the tumoricidal state. The effect of encapsulation of recombinant human macrophage colony-stimulating factor (M-CSF) in Man-MLV on prolongation of survival of monocytes was examined. Blood monocytes that had been incubated for up to 21 days with Man-MLV containing 5–20 U of M-CSF per ml were effective in prolonging monocyte survival, but monocytes that had been incubated in medium with less than 50 If/ml of M-CSF or with control MLV containing 5–10 U of M-CSF showed no increase of monocyte survival over that in medium alone. Addition of rabbit anti-M-CSF antiserum did not affect survival prolongation of monocytes by M-CSF encapsulated in Man-MLV. We conclude that liposomes modified with cetylmannoside are far more effective than unmodified liposomes as a carrier to deliver biological response modifiers to human blood monocytes.     

Hämatologische oder hämostaseologische „Paraneoplasien“ als Prognosefaktoren?

Summary Paraneoplastic syndromes are early but seldom appearing remote effects of tumors. In contrast, hematological or hemostaseological tumor signs can be demonstrated nearly in every tumor patient, mostly, however, after prolonged disease. The signs result from interaction between tumor and host, they depend upon the monocyte-macrophage system and are mediated by interleukin-1. Therefore, strictly speaking, they are no paraneoplasias.By genetic instability and increasing heterogeneity, the tumor cell gradually overcomes this defence line and the clinical pictures of different metastatic diseases equalize slowly. Finally, main causes of death are equally occurring infectious and hemostaseological complications. They demonstrate the final breakdown of this defence system.

---

Abkürzungen BC Bronchialkarzinom - TG beta-Thromboglobulin - CPA cancer procoagulant activity - DIC disseminierte intravaskuläre Gerinnung - FDP Fibrin(ogen)-Spaltprodukte - FPA Fibrinopeptid A - IL-1 Interleukin-1 - PF4 Plättchenfaktor 4 - PDGF Plättchenwachstumsfaktor - t-PA Gewebstyp-Plasminogenaktivator - u-PA Urokinasetyp-Plasminogenaktivator Herrn Prof. Dr. N. Zöllner, München, zum 65. Geburtstag gewidmet     

输尿管梗阻及再通大鼠肾组织中单核-巨噬细胞相关因子动态表达

目的 探讨输尿管梗阻及再通大鼠肾间质纤维化发生和恢复过程中单核-巨噬细胞相关因子的动态表达。方法 将48只SD大鼠随机分成梗阻和再通两个实验部分,梗阻部分分为假手术组（sham,n=6）、单侧输尿管梗阻（UUO）3d（n=6）、UUO 7d（n=6）和UUO 14d（n=6）;再通部分分为双侧输尿管梗阻（RBUO）0d（n=6）、RBUO后再通3d（n=6）、RBUO后再通 7d（n=6）和RBUO 后再通14d（n=6）。术后3、7和14 d后处死取其肾脏组织。采用HE和Masson染色观察肾组织病理改变和间质纤维化程度;免疫组织化学染色检测肾组织内单核细胞趋化蛋白-1（MCP-1）、巨噬细胞克隆刺激因子（M-CSF）和活化巨噬细胞标志物CD68的表达水平;Real-time PCR检测MCP-1和M-CSF mRNA表达水平;ELISA测定TGF-β1含量。 结果 与Sham大鼠相比,UUO大鼠随着梗阻时间延长,纤维化程度加剧。同时TGF-β1水平明显升高。输尿管再通后,纤维化程度随时间延长明显减轻,且TGF-β1水平明显下调。UUO大鼠肾组织中,MCP-1和M-CSF mRNA和表达蛋白随梗阻时间延长而增加;梗阻再通后,MCP-1和M-CSF mRNA和蛋白表达随再通时间延长持续下降。MCP-1和M-CSF在UUO或再通大鼠肾组织中的表达与CD68呈现一致性变化趋势。 结论 输尿管梗阻后,M-CSF和MCP-1的动态表达反映单核-巨噬细胞的活化和聚集状态,这可能是间质纤维化发生十分重要的炎症基础。而输尿管再通可抑制活化和趋化的单核-巨噬细胞,控制炎症反应,缓解肾间质纤维化。     

炎性刺激下张应力对成骨细胞核心结合因子α1表达的影响

目的观察成骨细胞在牙龈卟啉菌脂多糖(Pg-LPS)刺激单核巨噬细胞上清培养下张应力对其核心结合因子α1(Runx2/Cbfα1)表达的影响。方法成骨细胞MC3T3-E1于Pg-LPS刺激单核巨噬细胞上清培养24h后,应用四点弯曲加力装置对细胞分别加载1000μstrain和3000μstrain循环单轴张应力0h、0.5h、1h、2h、3h、6h,采用实时荧光PCR检测细胞Runx2/Cbfα1mRNA的表达差异性。同时设非炎性刺激组为对照组。结果机械牵张力刺激下,炎性刺激组细胞和非炎性刺激组细胞Runx2/Cbfα1mRNA表达趋势相似,0.5h后升高,6h最高;炎性刺激组细胞各时点Runx2/Cbfα1mRNA表达低于非炎性刺激组(P<0.05);不同应力作用下,前3h细胞Runx2/Cbfα1mRNA表达未见明显差异,6h时3000μstrain组细胞表达高于1000μstrain组(P<0.05)。结论炎症刺激可抑制应力下成骨细胞Runx2/Cbfα1的表达,提示临床上对牙周炎静止期患者施力需谨慎。     

组织定居巨噬细胞在肿瘤微环境中的作用

肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)是肿瘤微环境中最主要的免疫细胞群之一,在肿瘤生长、血管生成和治疗等各环节发挥重要作用。以往研究认为肿瘤微环境中TAMs主要来源于循环单核细胞,但近期研究证实,起源于胚胎卵黄囊及胎肝的组织定居巨噬细胞也可以在肿瘤微环境中分化为TAMs,TAMs主要通过细胞增殖从而实现自我更新。文章就肿瘤微环境中该群TAMs来源、分化及其作用进行综述。     

单核巨噬细胞在慢性阻塞性肺疾病中的作用

慢性阻塞性肺疾病(COPD)是呼吸系统常见的慢性非特异性炎症,目前认为有包括单核巨噬细胞在内的多种炎性细胞的参与。单核巨噬细胞能够分泌、调节多种炎性介质和蛋白,并和其他炎性细胞相互作用,形成一个复杂的炎性网络,使COPD患者肺组织中大量炎性细胞聚集、浸润,肺内损伤与修复交替出现,引起肺泡壁破坏和肺纤维化。单核巨噬细胞在COPD的发病过程中发挥关键的作用。