Immunopathology of Schistosoma japonicum and S. mansoni infection in B cell depleted mice

To investigate the role of antibody in the pathogenesis of hepatic granulomas around schistosome eggs, mice were depleted of B cells by treatment from birth with anti-IgM serum and were subsequently infected with Schistosoma japonicum or S. mansoni. Anti-IgM treatment did not affect the development or fecundity of the worms or the larvae within the egg shells. Normal circumoval granulomas were present in the livers of B cell depleted mice 7 or 8 weeks after infection clearly indicating that antibody and immune complexes have no necessary role in the formation of granulomas. Hepatic fibrosis was also similar in B cell depleted and untreated mice at these times. Ten weeks after infection the size of S. japonicum egg granulomas in untreated mice had decreased but no change in the size of granulomas had occurred in B cell depleted mice, and hepatic fibrosis was more marked in treated than in untreated mice. Similar changes were noted in S. mansoni infected mice, assayed at 8 and at 12-13.5 weeks after infection. The effects of B cell depletion in the more chronic infections may be related to the absence of antibody but could also be caused by an influence on B cell-dependent suppressor T cells.     

Variation of hepatic fibrosis and granuloma size among mouse strains infected with Schistosoma mansoni

To investigate the relation between the size of circumoval granulomas and hepatic fibrosis, a variety of mouse strains infected with Schistosoma mansoni were examined and the number of eggs in the tissues, the fibrotic responses to the eggs, and the volume of the granulomas were determined. Marked differences in granuloma volume and in hepatic fibrosis were found between mouse strains, and those strains with the largest granulomas also showed the most hepatic fibrosis. On the other hand no significant correlation between granuloma size and hepatic fibrosis was found in the progeny of the F2 generation and backcrosses between F1 mice and the parental strains when crosses were made between Nmri mice (high granuloma volume and high fibrosis) and C57BL/6 mice (low granuloma volume and low fibrosis). Hepatic fibrosis per egg decreased with increasing infection intensity while granuloma volume was unaffected, indicating that fibrosis and granuloma size are at least in part modulated by different factors. The number of eggs found in the tissues per worm pair and the proportion of eggs in the liver also decreased as infection intensity increased. Some influence of the major histocompatibility complex on both granuloma size and fibrosis was found. Congenic mice on the C57BL/10 and C3H/HeSn backgrounds showed larger granulomas in H-2b than in H-2k mice, but no such correlation was found in comparing C57BL/6 mice with B6.H-2k mice. Less hepatic fibrosis was found in B10.M (H-2f), B10.SM (H-2v), and B10.RIII (H-2r) animals than in C57BL/10 mice. The regulation of granuloma size and of hepatic fibrosis is clearly complex and involves genes both outside of and within the major histocompatibility complex.     

Anti-interleukin-4 treatment diminishes secretion of Th2 cytokines and inhibits hepatic fibrosis in murine schistosomiasis japonica

Anti-interleukin-4 (IL-4) treatment o/"Schistosoma japo-nicum-infected mice markedly inhibited in vitro secretion of the Th2 cytokines IL-4 and IL-5 from antigen-stimulated spleen cells, but enhanced the secretion of the Th1 cytokine IFN-γ. IL-2 secretion was unaffected. Hepatic fibrosis was markedly diminished in anti-IL-4-treated-mice at ten weeks of infection while granulomas around S. japonicum eggs in the livers were slightly-to-moderately increased in size. The number of eggs per worm pair in the tissues and feces did not differ significantly in treated and untreated mice. These findings suggest that Th2 cytokine responses are important in the genesis of schistosomal hepatic fibrosis.     

Persistence of hepatic fibrosis and tissue eggs following treatment of Schistosoma japonicum infected mice

The persistence of hepatic fibrosis and of Schistosoma japonicum eggs in the tissues of mice was examined after chemotherapy. C57BL/6 mice infected with a Philippine strain of S. japonicum were treated with praziquantel or amoscanate 7 or 8 weeks after infection. Groups of mice were killed at the time of treatment and 3, 8, 26, and 52 weeks later. The number of eggs per worm pair in the tissues did not change during the year after treatment. However, S. japonicum eggs injected into the tail vein were gradually destroyed in the lungs. Hepatic fibrosis increased in the 1st few weeks after treatment and did not change significantly thereafter. Praziquantel, but not amoscanate, had an immediate toxic effect on the most mature eggs in the tissues which was accompanied by a marked but transient decrease in eggs passed in the feces. Less mature eggs appeared unaffected by the drug and the passage of eggs in the feces resumed as these matured. Egg passage then ceased as the supply of viable eggs was exhausted.     

Alterations in influence of granuloma-derived cytokines on fibrogenesis in the course of murine Schistosoma mansoni infection

Schistosomiasis is the main cause of hepatic fibrosis worldwide, yet its pathogenesis remains unknown. We previously reported that conditioned medium from cultures of hepatic egg granulomas (isolated from mice acutely infected with Schistosoma mansoni) can stimulate fibroblast proliferation and matrix production in vitro. We have proposed that initiation of hepatic fibrosis in this infection might be under the control of granuloma-derived cytokines. We now report that conditioned medium from cultures of schistosomal egg granulomas isolated from liver of chronically infected mice has reduced fibrogenic activity compared with medium from cultures of granulomas obtained from more acutely infected mice. In related studies, we adoptively transferred splenocytes from infected mice and examined the fibrogenic activity in culture supernatants of hepatic egg granulomas isolated from the recipients. Those prepared from recipients of splenocytes from chronically infected mice contained substantially less fibrogenic activity than did those from recipients of splenocytes of acutely infected mice. These findings suggest that the fibrogenic influence of schistosomal egg granuloma products decreases during the course of chronic murine S. mansoni infection. Furthermore, our preliminary findings suggest that immunoregulatory cells may be responsible for the down-regulation of this influence. Previous observations indicating that in murine schistosomiasis hepatic collagen and hyaluronate synthesis and deposition are elevated in acute but not chronic infection might be explained on the basis of our observations.     

Comparison of immune responses of Schistosoma mansoni-infected mice with distinct chronic forms of the disease

BACKGROUND: Schistosoma mansoni-infected mice tend to present with either one of two different hepatic pathological patterns during chronic infection: periportal fibrosis (PF) with portal concentration of periovular granulomas and fibrosis or isolated granulomas (IG), with scattered periovular granulomas within the liver. These are models for the two clinical presentations of schistosomiasis, the severe hepatosplenic and the mild intestinal forms. In the present work, we examined the relationship between the development of these histopathological aspects and immunological markers in S. mansoni-infected mice. Although BALB/c mice with PF and IG had similar egg numbers in the liver, PF mice had higher liver collagen contents than mice with IG. Cultured spleen cells from mice with PF and IG had similar proliferation 20 and 40 weeks after S. mansoni infection upon stimulation with parasite egg antigen (SEA) or mitogen (Con A). Production of IL-4 upon SEA stimulation was higher in cell cultures from mice with PF, whereas IL-5 and IFN-gamma levels were not statistically different between PF and IG groups. Mice with IG had similar serum concentrations of total IgE and anti-SEA IgG1, IgG2a, IgG2b and IgG3 compared to sera from PF mice. Levels of IgG1 and IgG2a antibodies were the highest and the lowest detected, respectively. In conclusion, isogenic BALB/c mice infected with S. mansoni that develop periportal fibrosis or isolated granulomas have similar immunological patterns despite the two pathologic forms of schistosomal liver fibrosis.     

Hybridization of Schistosoma mansoni and Schistosoma japonicum in mice

Crossing experiments in mice with two human species of Schistosoma japonicum (Taiwan strain) and Schistosoma mansoni (Puerto Rican strain) were performed. The hybrid miracidia from the cross between female S. japonicum and male S. mansoni infected both Biophalaria glabrata and Oncomalania h. chiui. However, those from the reciprocal crossing could infect only B. glabrata. B. glabrata infected with hybrid miracidia of female S. mansoni x male S. japonicum survived up to 30 days while those infected with miracidia of S. mansoni remained alive for more than 100 days after the first shedding of cercariae. Relatively few hybrid eggs reached maturity either in tissues or in the feces of infected mice. A low percentage of F1 eggs hatched and the infectivity of F1 miracida was also low. Morphology and behavior of hybrid eggs, miracidia, cercariae, and adults were similar to the maternal species. The daily egg production of the hybrid worm pair was less than that of the normal one. The observations in the present study may be attributed to the maternal effects. However, the phenomenon of parthenogenesis in schistosomes cannot be confirmed.     

Variable maturation and oviposition by female Schistosoma japonicum in mice: the effects of irradiation of the host prior to infection

The maturation of female Schistosoma japonicum was found to vary greatly within each of two Philippine strains of this parasite and some females did not contain uterine eggs 7 to 15 weeks after infection while others contained numerous eggs before the fifth week of infection. It was found that female worms containing less than 20 uterine eggs contributed little to the accumulation of eggs in the tissues of infected mice. Such worms also generally appeared to be immature. The variable rate of maturation of worms is likely to have profound effects on the immune reactions of mice as well as on the pathologic response to infection. Systematic delay in oviposition was serendipitously found in worms from mice which had been irradiated for other purposes prior to exposure to S. japonicum, and from the fourth to the sixth week after infection egg production by worms in irradiated mice lagged well behind that in intact mice. Seven to 10 weeks after infection these worms were laying normal numbers of eggs, as judged by egg passage per worm pair in the feces and the accumulation of eggs in the tissues. S. mansoni developed normally in irradiated mice.     

T细胞缺陷对日本血吸虫感染宿主存活及肝脏虫卵肉芽肿形成的影响

目的观察T细胞缺陷对日本血吸虫感染宿主存活时间,肝脏虫卵肉芽肿形成及日本血吸虫雌虫产卵的影响。方法T细胞缺陷小鼠（裸鼠）和BALB／c小鼠各20只,每只感染日本血吸虫尾蚴（25±1）条,记录感染后存活时间。感染后第42d,从2组存活小鼠中各随机取7只剖杀,取肝组织,计数肝内虫卵;制作肝组织切片,观察虫卵肉芽肿病理学变化,并测量单个虫卵肉芽肿直径。结果20只裸鼠感染日本血吸虫后46d全部死亡。裸鼠肝组织中的雌虫产卵数为（4759．5±2161．3）个／条,BALB／c小鼠为（7323．4±2254．6）个／条,差异有统计学意义（P％0．05）。裸鼠肝脏中单个虫卵肉芽肿直径为（138．4±31．9）μm,与感染组BALB／c小鼠（316．4±68．2）μm比较,差异有统计学意义（P〈0．01）,且不能形成典型局限性虫卵肉芽肿,肉芽肿内嗜酸性粒细胞明显减少,周围肝组织伴有大面积坏死。结论宿主T细胞对虫卵肉芽肿的形成和维持感染宿主的生存具有重要作用。     

日本血吸虫再感染小鼠模型的实验观察

目的观察反复感染小鼠化疗后抗日本血吸虫再感染的效果,为分析人群再感染的规律提供实验依据。方法采用Ｃ５７ＢＬ／６纯系小鼠建立日本血吸虫再感染的动物模型,于攻击感染后４５天剖杀小鼠,计算小鼠体内成熟成虫数及肝虫卵数。结果与对照组相比较,攻击感染后再感染小鼠体内成熟成虫和肝虫卵数较对照组明显减少,减虫率达２７．１３％,减卵率为３６．６２％,肝脏虫卵芽肿数量也明显减少。结论表明反复感染小鼠经过治疗后可产生一定程度的对再感染的抵抗力,从而间接地验证了人群再感染的现场观察结果。     

日本血吸虫调宁蛋白样蛋白P14基因DNA疫苗对小鼠免疫保护作用研究

摘 要：目的 研究日本血吸虫调宁蛋白样蛋白P14基因DNA疫苗对小鼠免疫保护作用。 方法 制备无内毒素DNA疫苗,用于免疫小鼠。将雌性BALB/c小鼠随机分为4组,每组10只。生理盐水组给予100 μl/鼠/次;空质粒组100 μg/鼠/次、pcDNA3.1(+)-SjP14组、pcDNA3.1(+)-SjP14 + pcDNA3.1(+)-SjGST组分别经肌肉给予100 μg/鼠/次;同上每2周免疫一次,共3次。末次免疫后2周,经腹部皮肤感染日本血吸虫尾蚴（30±1）条/鼠。尾蚴攻击6周后解剖小鼠,收集成虫和血清,计算减虫率并检测血清IgG1、IgG2a及总IgG;同时留取肝脏,部分消化后在显微镜下行虫卵计数,计算减卵率,部分肝脏用于组织病理学分析（HE染色法）,观察肝细胞变化及肉芽肿情况。结果 与NS对照组比较,pcDNA3.1(+)-Sj P14p核酸疫苗组减虫率和减卵率分别达到45.1%（P<0.05）和62.0%（P<0.001）;SjP14核酸疫苗与SjGST核酸疫苗联合免疫组减虫率和减卵率分别提高至56.3%（P<0.01）和73.9%（P<0.001）;SjGST和SjP14 组减虫率大于SjP14疫苗组,但两组之间差异无显著性（P＞0.05）; SjGST和SjP14组减卵率明显大于SjP14疫苗组, 两组之间差异有显著性（P<0.001）。SjGST和SjP14组与SjP14组血清IgG1、IgG2a及总IgG水平在免疫6周、12周后均较对照组显著提高（P<0.01）,但SjGST和SjP14组与SjP14之间差异无显著性（P＞0.05）。肝组织切片镜下显示,pcDNA3.1(+)-SjP14组肝脏病变较生理盐水组和空质粒组明显减轻,pcDNA3.1(+)-SjP14 + pcDNA3.1(+)-SjGST组肝脏损伤程度最轻,虫卵肉芽肿周围炎症反应轻,肉芽肿面积较小。结论 pcDNA3.1(+)-Sj P14核酸疫苗有一定程度的抗血吸虫感染作用,pcDNA3.1(+)-SjP14与pcDNA3.1(+)-SjGST疫苗联合免疫能增强小鼠对血吸虫感染的保护。     

Evaluation of hepatic fibrosis after oxamniquine therapy of murine schistosomiasis.

Chemical and histological indices of liver fibrosis were measured after eight, 18 and 28 weeks in mice infected with Schistosoma mansoni and treated at eight weeks with oxamniquine, in mice infected with S. mansoni and not treated and in mice not infected with S. mansoni. Total worm burdens and liver egg counts were determined in the infected mice to determine severity of infection. Treatment with oxamniquine resulted in near total eradication of S. mansoni worms after 10 weeks and in their complete killing and marked reduction of eggs in the liver at 10 and 20 weeks. Liver fibrosis 10 weeks after oxamniquine treatment was not significantly different than in the untreated, infected group but there was no progression between 10 and 20 weeks after oxamniquine treatment. Fibrosis did however increase between 10 and 20 weeks in the untreated infected group. In the murine model, oxamniquine is an effective treatment for S. mansoni and prevents progression of liver fibrosis.     

乙型肝炎病毒感染和血吸虫感染对肝纤维化的影响

目的分析乙型肝炎病毒（HBV）感染和血吸虫感染对肝纤维化的影响。方法肝纤维化脾大脾亢患者59例,取肝组织进行肝纤维化病理分期并查肝组织血吸虫虫卵;采用酶联免疫吸附试验（E1。ISA）检测血清乙肝两对半,同时观察患者临床症状及实验室指标包括血常规、肝功能及血清胶原蛋白（HA）,血小扳转化生长因子BB（PDGF-BB）和金属蛋白酶组织抑制因子1（TIMP-1）水平。分析乙肝阳性与乙肝阴性肝纤维化患者之间,肝组织血吸虫虫卯阳性与虫卵阴性肝纤维化患者之间的肝纤维化程度、临床及实验室检查指标的差异,并分析影响肝纤维化程度的相关因素。结果乙肝肝纤维化患者肝功能显著异常,其血清HA和PDGF—BB分别为（1．03±0．35）ng／ml和（0．31±0．04）ng／ml,与单纯血吸虫病肝纤维化患者的（0．69±0．20）ng／ml和（0．11±0．03）ng／ml比较差异均有统计学意义（P〈0．01）。肝组织虫卯阴、阳性患者问的肝纤维化程度差异无统计学意义（x2=2．266,P〉0．05）;肝纤维化严重程度与乙肝感染相关（B=0．382,P〈0．05）,与肝脏血吸虫虫卯数无相关性（P〉0．05）。结论乙肝比血吸虫病对肝纤维化的影响更严重,临床上应先确定肝纤维化的病因,以指导临床治疗。     

Immunopathology of Schistosoma japonicum infection in athymic mice

Athymic (nu/nu) mice and heterozygous littermate controls (nu/+) were examined 7 and 10 weeks after infection with 10 cercariae of Schistosoma japonicum. Schistosome infection developed normally in both groups of mice and eggs were produced in normal numbers. Nu/nu mice developed small circumoval granulomas with minimal fibrosis while nu/+ mice developed large fibrotic granulomas. Unlike the mononuclear responses to S. mansoni eggs at 7 weeks, those to S. japonicum often were abscess like with narrow rims of liver cell necrosis or microvesicular fatty change. However, evolving granulomas in nu/+ mice were enriched with eosinophils, epithelioid macrophages, immature granulocytes and plasma cells, all scarce in the corresponding nu/nu lesions as were fibroblasts and collagen fibres, thus accounting for their smaller mean size and better healing. Our aggregate evidence shows that normal granuloma formation and cellularity in S. japonicum infection is controlled by T-cells as is the case for S. mansoni, and not by antibodies or immune complexes.     

日本血吸虫重组抗原rSj14-3-3免疫保护作用的初步研究

目的　初步探讨重组信号蛋白 14 3 3及 14 3 3与GST融合蛋白抗日本血吸虫尾蚴感染和抗血吸虫病的免疫保护作用。　方法　用rSj14 3 3和rSj14 3 3 /SjGST免疫BALB/c小鼠 ,日本血吸虫尾蚴经腹部皮肤攻击感染 ,收集实验组与对照组成虫和虫卵 ,计算减虫率和减卵率 ;间接ELISA法测定实验组与对照组小鼠免疫前、后血清中特异性IgG抗体水平的变化 ;显微镜下测量并比较实验组与对照组肝脏切片上单个虫卵肉芽肿大小 ,观察两种重组抗原对小鼠肝脏肉芽肿形成的影响。　结果　上述两种重组抗原在尾蚴攻击感染后的减虫率分别为 3 1.93 %和 3 4.3 9% ;每克肝组织减卵率分别为 5 3 .2 4%和 60 .0 6% ,每对成虫减卵率分别为 3 3 .3 9%和 40 .48% ;免疫前各组血清IgG抗体A值差异无显著性 ,免疫后实验组血清IgG抗体A值明显高于对照组 ;实验组小鼠肝脏虫卵肉芽肿平均直径比对照组分别下降3 5 .2 3 %和 46.13 %。　结论　信号蛋白 14 3 3在抗感染和抗病免疫中具有保护作用 ,复合多价疫苗的免疫保护作用可能优于单价疫苗。     

桑黄多糖缓解日本血吸虫感染小鼠氧化应激及 肝纤维化的实验研究

目的　探讨桑黄醇提多糖（PPI）对日本血吸虫感染小鼠氧化应激、肝肉芽肿和肝纤维化的改善作用。方法　采用日本血吸虫尾蚴玻片贴腹感染法建立日本血吸虫肝病小鼠模型。设健康对照组（A组）、感染对照组（B组）、PPI单独治疗组（C组）、吡喹酮单独治疗组（D组）和PPI加吡喹酮混合治疗组（E组），每组各10只小鼠；除A组外，其他各组每只小鼠感染（30 ± 2）条尾蚴。自感染后42 d开始，D、E组小鼠灌胃给予500 mg/kg吡喹酮，连续2 d；C、E组给予400 mg/kg PPI灌胃，连续给药30 d。HE染色观察小鼠肝组织病理学改变，测定小鼠血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、透明质酸（HA）、层黏连蛋白（LN）及小鼠肝组织匀浆中丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH?PX）、谷胱甘肽还原酶（GSH?R）、谷胱甘肽（GSH）含量，采用免疫组化技术检测小鼠肝组织中转化生长因子?β（TGF?β）、α?平滑肌肌动蛋白（α?SMA）表达水平，采用实时荧光定量PCR检测Nrf2、Gsta4基因表达水平。结果　日本血吸虫感染但未予治疗小鼠出现典型血吸虫病肝病病理改变，PPI干预后能有效减轻小鼠肝虫卵肉芽肿及胶原沉积。血吸虫病肝病小鼠肝脏脂质过氧化加剧，诱导了氧化应激，小鼠血清中MDA含量增加，GSH和各种抗氧化酶含量下降。与B组相比，PPI治疗抑制了脂质过氧化，提高了GSH含量，恢复了抗氧化酶活性。此外，PPI治疗可抑制TGF?β信号通路，提升Nrf2、Gsta4基因表达水平。结论　PPI在治疗血吸虫病肝纤维化方面发挥重要作用，其内在机制可能是通过上调Nrf2和Gsta4基因表达、改善氧化应激损伤，从而抑制肝脏虫卵肉芽肿形成和肝纤维化。     

桑黄多糖缓解日本血吸虫感染小鼠氧化应激及 肝纤维化的实验研究

目的　探讨桑黄醇提多糖（PPI）对日本血吸虫感染小鼠氧化应激、肝肉芽肿和肝纤维化的改善作用。方法　采用日本血吸虫尾蚴玻片贴腹感染法建立日本血吸虫肝病小鼠模型。设健康对照组（A组）、感染对照组（B组）、PPI单独治疗组（C组）、吡喹酮单独治疗组（D组）和PPI加吡喹酮混合治疗组（E组）,每组各10只小鼠;除A组外,其他各组每只小鼠感染（30 ± 2）条尾蚴。自感染后42 d开始,D、E组小鼠灌胃给予500 mg/kg吡喹酮,连续2 d;C、E组给予400 mg/kg PPI灌胃,连续给药30 d。HE染色观察小鼠肝组织病理学改变,测定小鼠血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、透明质酸（HA）、层黏连蛋白（LN）及小鼠肝组织匀浆中丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH?PX）、谷胱甘肽还原酶（GSH?R）、谷胱甘肽（GSH）含量,采用免疫组化技术检测小鼠肝组织中转化生长因子?β（TGF?β）、α?平滑肌肌动蛋白（α?SMA）表达水平,采用实时荧光定量PCR检测Nrf2、Gsta4基因表达水平。结果　日本血吸虫感染但未予治疗小鼠出现典型血吸虫病肝病病理改变,PPI干预后能有效减轻小鼠肝虫卵肉芽肿及胶原沉积。血吸虫病肝病小鼠肝脏脂质过氧化加剧,诱导了氧化应激,小鼠血清中MDA含量增加,GSH和各种抗氧化酶含量下降。与B组相比,PPI治疗抑制了脂质过氧化,提高了GSH含量,恢复了抗氧化酶活性。此外,PPI治疗可抑制TGF?β信号通路,提升Nrf2、Gsta4基因表达水平。结论　PPI在治疗血吸虫病肝纤维化方面发挥重要作用,其内在机制可能是通过上调Nrf2和Gsta4基因表达、改善氧化应激损伤,从而抑制肝脏虫卵肉芽肿形成和肝纤维化。     

小鼠日本血吸虫肝虫卵肉芽肿模型的建立

本文报告应用腹腔注射SEA致敏C57BL/6小鼠,继之经脾脏攻击注射虫卵的方法,建立了小鼠日本血吸虫肝虫卵肉芽肿模型,并与自然感染模型作比较.结果证明,SEA致敏组小鼠肝虫卵肉芽肿发生率为100%.其肉芽肿的形态、细胞组成、转化发展过程及单虫卵肉芽肿的直径和面积均与自然感染模型相似.本实验表明经脾脏注射虫卵及SEA致敏建立小鼠日本血吸虫肝虫卵肉芽肿模型是一种良好的肉芽肿实验动物模型.     

Fibroblast stimulation in schistosomiasis. I. Stimulation in vitro of fibroblasts by soluble products of egg granulomas

To gain further understanding of the pathogenesis of hepatic fibrosis in schistosomiasis, the interaction between egg granulomas and fibroblasts was investigated in an in vitro model. Egg granulomas isolated from livers of mice infected with Schistosoma mansoni or Schistosoma japonicum and cultured in vitro released a nondialyzable substance which stimulated proliferation in resting dermal fibroblasts. The release of the fibroblast-stimulating substance remained relatively constant during the first 48 hr of incubation with granulomas, during which time granulomas remained metabolically active in vitro. A dialyzable molecule(s) in granulomas supernatants interfered with fibroblast uptake of [3H]thymidine in vitro but did not inhibit cellular division. Granulomas supernatants also stimulated fibroblast secretion of prostaglandin E2 and caused an elevation in intracellular levels of cyclic adenosine monophosphate.     

曼氏血吸虫感染鼠肝脏虫卵肉芽肿反应及胶原含量定量测定

应用形态计量学方法和化学染色法 ,分别对 6个品系小鼠定量感染曼氏血吸虫后 7.5 wk的肝脏石蜡切片中虫卵肉芽肿面积和肝脏胶原纤维含量进行了定量观察。结果表明 ,感染鼠肝脏虫卵肉芽肿面积在不同种系小鼠间显示出一定差别 ,肝脏胶原含量较对照组均有明显增加。经相关分析 ,不同种系感染鼠肝脏虫卵肉芽肿面积与肝脏胶原含量间不存在相关关系。鉴于虫卵肉芽肿形成与肝纤维化过程在时相上的差别 ,提示两者受不同的免疫病理机制决定