Gestation and breastfeeding in schistosomotic mice differentially alters the expression of histone deacetylases (HDACs) in adult offspring

BACKGROUND Breastfeeding or gestation in schistosomotic mothers can cause long-term alterations in the immune response of offspring. OBJECTIVES Evaluate the expression of histone deacetylases (HDACs) (all classes), the production of cytokines by T and B lymphocytes and macrophages, and the frequency of CD4+CD25+FoxP3+-cells in adult offspring born and/or suckled by schistosomotic mothers. METHODS We harvested splenocytes from offspring born to (BIM), suckled by (SIM), or born to/suckled by (BSIM) schistosomotic mothers and animals from noninfected mothers (Control) at seven-weeks old and cultured them with/without Concanavalin A. HDAC expression was evaluated by real-time quantitative polymerase chain reaction (qPCR), and cytokines and membrane markers were evaluated by fluorescence-activated cell sorting (FACS). FINDINGS Compared to Control, BIM mice showed increased expression of HDAC9 and frequency of CD4+IL-10+-cells. The SIM group had increased expression of HDAC1, HDAC2, HDAC6, HDAC7, HDAC10, Sirt2, Sirt5, Sirt6, and Sirt7. The BSIM group only had increased HDAC10 expression. The SIM and BSIM groups exhibited decreased frequencies of CD4+IL-4+-cells and CD4+CD25+FoxP3+-cells, along with a higher frequency of CD14+IL-10+-cells and an increase in CD45R/B220+IL-10+-cells. The BSIM group also showed a high frequency of CD4+IL10+-cells. MAIN CONCLUSIONS Breastfeeding induced the expression of HDACs from various classes involved in reducing inflammatory responses. However, gestation enhanced the expression of a single HDAC and breastfeeding or gestation appears to favour multiple IL-10-dependent pathways, but not cells with a regulatory phenotype.

Superimposing a high-fat diet on schistosoma mansoni infection affects renin-angiotensin system components in the mouse kidney

Abstract INTRODUCTION: The levels of the full-length form of the (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), may be reduced in the membranes of kidneys in renal diseases. This study aimed to investigate the RAS components in the kidneys of mice submitted to a combination of a high-fat diet and Schistosoma mansoni infection. METHODS: Female BALB/c mice were maintained on a control or high-fat diet from 3 weeks of age. After 10 weeks on the designated diets, half the mice in each group were infected with S. mansoni cercariae. The blood and kidneys were harvested 8 weeks after infection. RESULTS: The high-fat diet increased the number of eggs in the feces and the number of adult worms in the mesenteric bed. Schistosoma mansoni infection reduced the plasma levels of glucose, triglycerides, and HDL cholesterol in the control and high-fat diet groups. In mice on the control diet, S. mansoni infection resulted in increased expression of IL-6 in the kidneys; however, in mice on the high-fat diet, the levels of IL-6 were reduced and those of superoxide anions were increased. The RAS components evaluated were ACE2, renin, PRR, AT1R, and AT2R, and the levels of PRR were found to be reduced in the kidneys of infected mice on the high-fat diet. CONCLUSIONS: The finding regarding PRR is not yet clear. However, combining a high-fat diet and S. mansoni infection resulted in increased oxidative stress in the kidney that can aggravate hypertension as well as its associated complications.

Biochemical and histological changes in liver of Nectomys squamipes naturally infected by Schistosoma mansoni / Alterações na bioquímica e histologia do fígado de Nectomys squamipes naturalmente infectado por Schistosoma mansoni

The South American water rat Nectomys squamipes is a wild mammal reservoir of Schistosoma mansoni in Brazil. In the present study, wild rodents were collected in the field and categorized into two groups: infected and uninfected by S. mansoni. Blood was collected to analyze changes in the serum glucose level (mg/dL) and liver fragments were used to determine the hepatic glycogen content (mg of glucose/g tissue). The histological examination showed inflammatory granulomatous lesions in different phases of development in the liver of rodents naturally infected with S. mansoni, in some cases with total or partial occlusion of the vascular lumen. Early lesions were characterized by the presence of inflammatory infiltrate around morphologically intact recently deposited eggs. Despite the significance of these histological lesions, the biochemical changes differed in extent. N. squamipes naturally infected by S. mansoni showed no variation in hepatic glycogen reserves. These findings were accompanied by a significant increase in plasma glucose contents, probably as a consequence of amino acids deamination, which are degraded, resulting in the formation of intermediates used as precursors for the glucose formation, without compromising the reserves of liver glycogen. In the wild, naturally infected N. squamipes can maintain S. mansoni infections without undergoing alterations in its carbohydrate metabolism, which minimizes the deleterious effects of S. mansoni.

Nectomys squamipes é um mamífero silvestre reservatório de Schistosoma mansoni no Brasil. No presente estudo, os roedores silvestres, colhidos no campo, foram classificados em dois grupos: infectado e não infectado por S. mansoni. O sangue foi colhido para análise da alteração no nível de glicose sérico (mg/dL) e fragmentos de fígado foram usados para determinar o conteúdo de glicogênio hepático (mg de glicose/g tecido). A análise histológica demonstrou lesões granulomatosas em diferentes fases de desenvolvimento no tecido hepático dos roedores naturalmente infectados com S. mansoni, localizados principalmente na região periportal, com total ou parcial oclusão do lúmen vascular. As lesões foram caracterizadas por presença de infiltrado inflamatório ao redor de ovos morfologicamente intactos recentemente depositados. Apesar da grande significância das lesões histológicas, as alterações bioquímicas não diferiram no mesmo grau. N. squamipes naturalmente por S. mansoni não apresentaram variação na reserva de glicogênio hepático. Esses achados foram acompanhados pelo aumento significativo nos conteúdos de glicose plasmática, provavelmente como consequência ao processo desaminativo de aminoácidos, que passam a ser degradados notadamente para a formação de glucose, sem contudo comprometer a reserva de glicogênio hepático. Em condições naturais a infecção de S. mansoni pode ser mantida usando N. squamipes como hospedeiro definitivo, sem alterações significativas nos conteúdos de glicogênio hepático, minimizando os efeitos deletérios causados por S. mansoni nos roedores N. squamipes naturalmente infectados.

Immunohistochemical expression of oestrogen and progesterone receptors during experimental acute and chronic murine Schistosomiasis mansoni / Expressão imunohistoquímica de receptores para estrogênio e progesterona nas fases aguda e crônica da esquistossomose mansônica experimental em camundongos

INTRODUCTION: The responsibility of Schistosoma mansoni in female infertility is still controversial. This study was conducted to evaluate the effect of acute and chronic schistosomiasis mansoni infection on the endometrium using immunohistochemical analysis of uterine hormone receptor expression. METHODS: Twenty-four nonpregnant swiss albino mice were divided into three groups: control, noninfected; acute; and chronic Schistosoma mansoni infection. Histological sections of uterine specimens were examined by light microscope with an image analyzing system to detect structural histological, estrogen receptor (ER) and progesterone receptor (PR) expression in the endometrium. RESULTS: No secretory phase was detected in the endometrium in acute and chronic Schistosoma infection. Hormone receptor expression (ER and PR) showed statistically significant differences among the groups (p< 0.05), with significant low ER hormone expression in chronic infection, compared to control proliferative, control secretory and acute infection cases, and statistically significant high PR expression in both acute and chronic infection cases compared to the control secretory cases (p< 0.05). CONCLUSIONS: Schistosomiasis mansoni seems to have an important impact on the hormone expression of affected women. Further studies to explore the mechanism of such changes are recommended.

INTRODUÇÃO: A responsabilidade do Schistosoma mansoni em esterilidade feminina é ainda controversa. Este estudo é conduzido para avaliar o efeito da esquistossomose mansoni aguda e crônica no endométrio usando análise de imuno-histoquímíca da expressão de receptor hormonal uterina. MÉTODOS: Vinte e quatro camundongos fêmeas albinas suíças não grávidas foram divididas em 3 grupos (controle não-infectado, grupos agudos e crônicos infeccionados com Schistosoma mansoni). As seções histológicas de espécimes uterinos foram examinadas por microscópio leve com imagem, analisando sistema para detectar no endométrio expressões histológicas estruturais, receptor de estrogênio (ER) e receptor de progesterona (PR). RESULTADOS: Nenhuma fase secretora foi detectada no endométrio com infecção aguda e crônica de Schistosoma. A expressão hormonal de receptor (ER e PR) mostrou diferenças estatisticamente significantes entre grupos diferentes (p<0,05) com baixa significativa hormonal de ER com infecção crônica (comparado com controle proliferativo, controle secretório e casos agudos de infecção) e alta expressão de receptor de PR estatisticamente significativa em casos tanto agudos e crônicos de infecção como comparado com os casos de controle secretório (P <0,05). CONCLUSÕES: A esquistossomose mansoni parece ter um maior impacto em expressão hormonal das mulheres afetadas. Mais estudos para explorar o mecanismo de tais mudanças são recomendados.

High fat diet has a prominent effect upon the course of chronic schistosomiasis mansoni in mice

This study investigated whether a long-term high-fat diet has an effect on the outcome of chronic murine schistosomiasis mansoni compared to a standard diet. Swiss Webster female mice (3 weeks old) were fed each diet for up to six months and were then infected with 50 Schistosoma mansoni cercariae. Their nutritional status was assessed by monitoring total serum cholesterol and body mass. Infected mice were examined 6-17 weeks post infection to estimate the number of eggs in faeces. Mice were euthanised the next day. Total serum cholesterol was lower in infected mice in comparison to uninfected controls (p = 0.0055). In contrast, body mass (p = 0.003), liver volume (p = 0.0405), spleen volume (p = 0.0124), lung volume (p = 0.0033) and faecal (p = 0.0064) and tissue egg density (p = 0.0002) were significantly higher for infected mice fed a high-fat diet. From these findings, it is suggested that a high-fat diet has a prominent effect on the course of chronic schistosomiasis mansoni in mice.

Carbohydrates detection in the hepatic egg - granuloma system using lectin histochemistry

This study aims to evaluate the egg-granuloma system in hepatic tissues using lectin histochemistry in experimental Schistosomiasis. Eight Swiss mice were infected with a local strain of Schistosoma mansoni, being submitted forty days later to a perfusion after which slices of liver were prepared. The tissue samples were incubated with the following peroxidase conjugated lectins: Peanut agglutinin (PNA), Wheat Germ agglutinin (WGA), and Concanavalin A (Con A). All lectins recognized the glycoconjugates in the adult worm tegument. In the hepatic tissue, WGA presented the highest staining followed by PNA and Con A. The PNA presented the most intense staining of the egg-granuloma system while WGA stained the hepatic sinusoid cells and Con A bound preferentially the fibrosis rings of granuloma and the surrounding hepatic parenquima. WGA and PNA indicated the presence of residues of N-acetyl-glucosamine and galactose in the surface of Schistosoma mansoni eggs in the hepatic granulomas. In conclusion, using PNA, Con A and WGA our study presented different aspects of the egg-granuloma and Tegument of Schistosoma mansoni as well as indicated differences in the peri-ovular granulomas indicating alterations in the cellular mechanism of expression of surface carbohydrates during progression of the Schistosomiasis.

El objetivo del estudio fue evaluar el sistema de los huevos de los granulomas en los tejidos hepáticos, utilizando histoquímica de lectinas esquistosomiasis. Ocho ratones suizos experimentales fueron infectados con una cepa local de Schistosoma mansoni y luego a los cuarenta días fueron sometidos a la perfusión y se prepararon cortes de hígado. Las muestras de los tejidos fueron incubadas con las siguientes peroxidasas lectinas conjugadas: aglutinina de maní (PNA), aglutinina de germenn de trigo (WGA), Concanavalin A (Con A). Todas las lectinas reconocieron las glicoconjugadas en el tegumento del gusano adulto. El tejido hepático con WGA presentó mayor coloración seguido de PNA y Con A. El PNA presentó la más intensa tinción de los huevos mientras el granuloma del sistema WGA tiñó las células hepáticas sinusoides y las Con A estuvieron siempre presentes en los anillos de la fibrosis y alrededor de los granulomas hepáticos del parénquima. WGA y PNA indicaron la presencia de residuos de N - acetil - glucosamina y galactosa en la superficie de los huevos de Schistosoma mansoni en los granulomas hepáticos de esquistosomiasis.

Cytokine profile associated with chronic and acute human schistosomiasis mansoni

The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma (IFN-³) was evaluated in 43 schistosomiasis patients with different clinical forms. Whole-blood cultures cytokine production in response to soluble egg antigen (SEA), soluble worm adult preparation (SWAP), mitogens, neutralizing antibodies or recombinant IL-13 were measured by ELISA. After SWAP stimulation, chronic patients, particularly hepatointestinals, produced higher levels of IL-4 in comparison with acute patients, suggesting the presence of a type 2 cytokine profile in these patients. Following SEA and SWAP stimulation, hepatosplenic (HS) patients showed increased levels of IFN-³ when compared with acute patients, indicating that HS disease in humans is associated with a type 1 cytokine response. The mechanisms of immune regulation are apparently different between the clinical stages of the disease, some of which are antigen-specific.

Four whole-istic aspects of schistosome granuloma biology: fractal arrangement, internal regulation, autopoietic component and closure

This paper centers on some whole-istic organizational and functional aspects of hepatic Schistosoma mansoni granuloma, which is an extremely complex system. First, it structurally develops a collagenic topology, originated bidirectionally from an inward and outward assembly of growth units. Inward growth appears to be originated from myofibroblasts derived from small portal vessel around intravascular entrapped eggs, while outward growth arises from hepatic stellate cells. The auto-assembly of the growth units defines the three-dimensional scaffold of the schistosome granulomas. The granuloma surface irregularity and its border presented fractal dimension equal to 1.58. Second, it is internally regulated by intricate networks of immuneneuroendocrine stimuli orchestrated by leptin and leptin receptors, substance P and Vasoactive intestinal peptide. Third, it can reach the population of ± 40,000 cells and presents an autopoietic component evidenced by internal proliferation (Ki-67+ Cells), and by expression of c-Kit+ Cells, leptin and leptin receptor (Ob-R), granulocyte-colony stimulating factor (G-CSF-R), and erythropoietin (Epo-R) receptors. Fourth, the granulomas cells are intimately connected by pan-cadherins, occludin and connexin-43, building a state of closing (granuloma closure). In conclusion, the granuloma is characterized by transitory stages in such a way that its organized structure emerges as a global property which is greater than the sum of actions of its individual cells and extracellular matrix components.

Preliminary results on the effects of CD40/CD40L interactions and SAC-induction on IFN-gamma expression in human schistosomiasis

In this communication the authors analyzed the pattern of expression of IFN-gamma as a surrogate type 1 response in different clinical forms of schistosomiasis in response to stimulation involving T-cell dependent and T-cell independent pathways, to investigate which pathways were functional in human schistosomiasis, and to further characterize the nature of Th1 response impairment in this parasitic disease

Extracellular matrix degradation in parasitic diseases

Fibrosis is an important manifestation of several parasitic diseases, but is not irreversible. A marked degree of extracellular matrix degradation can occur after cure of parasitism. Patients with the hepatosplenic form of schistosomiasis undergo considerable resorption of portal fibrosis monts or years after curative treatment as demonstrated by ultrasonography and pathological exmaination. 2. Studies of the post-treatment degradation of extracellular matrix in schistosomal periocular granulomas have demosntrated two forms of collagen degradation: in hepatic granulomas formed during early infection a rapid process occurs, with extracellular breakdown of fibers and internalization of collagen fragments, whereas during late infection, degradation in slow and is accompanied by focal electrondense and/or lytic changes. 3. Extensive extracellular matrix degradation and resorption occuring after curative treatment was recently described in the liver of a man with advanced visceral leishmaniasis and in the heart of mice with chronic Chagas' disease

Proteoglycans and glycosaminoglycans synthesized by the hepatic granulomas isolated from schistosome-infected mice and by a granuloma-derived connective tissue cell line

1. This paper summarizes our studies on proteglycans and glycosaminoglycans in the hepatic fibrosis occurring in schistosomiasis. 2. We have compared proteglycans and glycosaminoglycans isolated from schistosomal fibrotic granulomas with those obtained from the cellular and extracellular compartments of a murine cell line derived from schistosome-induced granulomas, primary cell line "GR". 3. Our results have shown some biochemical and structural similarities between proteglycans and glycosaminoglycans extracted from granulomas and those synthesized and secreted by GR cells, suggesting that cells may be the major cell population involved in synthesis and accumulation of these molecules in the schistosomal periovular granulomas in liver. Furthermore, we have shown that GR cells can function as an extramedullary myelopoietic stroma that mediates a long-term myeloid proliferation through an autocrine mechanism where the interaction between myelopoietic growth factors and cell-surface heparan sulfate proteoglycans was characterized

Myelopoietic competence of stroma composed of hepatic granuloma-derived connective tissue cells or skin fibroblasts

1. Connective tissue cells isolated form hepatic granulomas (GR cells), induced in mouse liver tissue by schistosomal infection, are able to sustain myelopoiesis, while other connective tissue cells such as skin fibroblasts (SF) are not. 2. We compared the ability of SF and GR cells sustain in vitro proliferation of the FDC-P1 myeloid cell line, dependent upon IL-3 or GM-CSF. 3. Only the GR stroma susteined the proliferation of co-cultured FDC-P1 cells. RT-PCR analysis showed that both cell lines expressed the message for GM-CSF, but not for IL-3. We showed that GM-CSF was produced by, and remained bound to the cell layer through heparan sulfate; this growth factor could be released by high-salt treatment in a biologically active form from both cell types. The same activity could be restored to NaCl-treated GR cells, but not to SF, by incubation with recombinant murine GM-CSF. 4. These results indicate that the ability of connective tissue cells to sustain myelopoiesis depends directly upon the capapcity of their heparan sulfate-bearing molecules to bind and present the GM-CSF to the target cells in a biologically active form. Alternatively, a yet unidentified set of cell layer-associated molecules may be required for the positive or negative control of the membrane-bound GM-CSF

Pathology of periportal fibrosis involution in human schistosomiasis

Optical and electron microscopical evidences of focal matrix degradation were frequently seen in liver sections of periportal fibrosis caused by schistosomiasis mansoni in man. The material came from 14 wedge hepatic biopsies taken from patients with chronic advanced hepatosplenic disease and undergoing operations for the relief of portal hypertension. Besides the presence of focal areas of rarefaction, fragmentation and dispersion of collagen fibers, the enlarged portal spaces also showed hyperplasia of elastic tissue and disarray of smooth muscle fibers following destruction of portal vein branches. Eggs were scanty in the tissue sections, and matrix degradation probably represented involuting changes related to the progressive diminution of parasite-related aggression, which occurs spontaneously with age or after cure by chemotherapy. The changes indicative of matrix degradation now described are probably the basic morphological counterpart of periportal fibrosis involution currently being documented by ultrasonography in hepatosplenic patients submitted to curative chemotherapy

Liver and serum solubre protein changes and pathomorphology in undernourished mice with acute schistonomiasis mansoni

No presente estudo os pesos corporal, hepático e esplênico; a morfologia patológica do fígado, baço e intestinos; e as modificaçöes das proteínas solúveis hepáticas e séricas, foram os parâmetros investigados em camundongos albinos Suíços desnutridos e infectados com S. mansoni. Os animais desnutridos näo infectados apresentaram relaçöes fígado/peso corporal e braço/peso corporal com valores menores do que os animais controles (grupo caseina a 22,60 por cento). Camundongos infectadas mostraram esses índices mais elevados, independentemente do tipo de dieta. O subgrupo de camundongos desnutridos infectados apresentou, no fígado, reaçäo periovular exsudativa persistente. O conteúdo de proteínas solúveis no fígado e no soro também mostrou-se reduzido nos camundongos infectados desnutridos. Diferença significativa foi detectada quanto às gamaglobulinas, comparando-se animais infectados com näo infectados alimentados com dieta controle II, valores mais altos ocorrendo no grupo dos infectados. Especula-se que os efeitos da má nutriçäo podem ser mais prejudiciais ao hospedeiro do que aqueles provocados pelo S. mansoni

Bioquímica da esquistossomose mansônica: envolvimento dos siderossomos nos processos inflamatórios hepáticos / Biochemistry of schistosomiasis mansoni: involvement of siderosomes in hepatic inflammatory processes

Os processos inflamatórios que se desenvolvem durante as etapas avançadas da esquistossomose mansônica foram relacionados, com o acúmulo de siderossomos, a capacidade dos ions ferrosos/férricos de desencadearem a formaçäo de radicais livres e a peroxidaçäo de lipídios membranáceos, assim como à diminuiçäo da estabilidade das membranas dos diversos componentes do comportamento lisossômico hepático. Os lisossomos isolados de figados de camundongos infectados por 100 cercárias, com 80 e 100 dias de infecçäo, foram respectivamente, 2,5 e quase 4 vezes mais frágeis que os controles, isolados de figados de camundongos näo infectados. A presença de siderossomos em grande quantidade foi demonstrada por espectrometria aos raios-X

Effect of experimental Schistosomiasis on 14C-4-cholesterol esterification by mouse liver homogenate

The effect of experimental schistosomiasis mansoni on cholesterol esterification by mouse liver homogenate was studied using 14C-4-cholesterol. The reaction was carried out in 0.85 ml containing 10 nCi labelled cholesterol (I64 nmol as an albumin-stabilized emulsion) with 30 mg tissue homogenate in 176 mM sodium phosphate buffer, pH 7.1, containing 59 micronM oleic acid, 0.3 mM CoASH and 8.8 mM ATP. In experiments with liver from infected mice(N = 22), the percentage of cholesterol esterification was 6.9 + or - 0.7%/h. This rate was 52% less than that observed in normal mice (14.4 + or - 0.6%/h, N = 21). The decrease may be due to the existence of inhibitors of the cholesterol esterifying in the infected liver, increased hydrolysis of cholesteryl esters or a decrease in the synthesis of the enzyme acyl CoA:cholesterol acyl transferase by the infected liver

Benzoic acid metabolism in presence of Schistosoma mansoni infection in mice.

The metabolism of benzoic acid was examined in S. mansoni infected CBA mouse. The result showed that control animals dosed with 150 mg/kg benzoic acid resulted in urinary excretion of two metabolites, hippuric acid and benzoic acid glucuronide. Administration of the same dose to animal carrying S. mansoni for a period of over 6 weeks resulted in decreased formation of hippuric acid and total elimination of benzoic acid by glucuronide pathway.

Bioquímica da esquistossomose mansônica: VII. Alteraçöes lipídicas das membranas lisossômicas durante a faze inicial da agressäo hepática / Biochemistry of schistosomiasis mansoni: VII. Changes of the lipid composition of lynsosomal membranes at the initialphase of liver injury

Com o intuito de se estudarem as alteraçöes nos teores lipídicos, constituintes das membranas lisossômicas, em fígados, durante a fase inicial da agressäo esquistossomótica, foram utilizados camundongos infectados com 30 cercárias e 30 dias de infecçäo. Os triaglicerídios passaram de 200 ñ 48 microng/mg de proteínas totais nos controles, para 165 ñ 22 microng/mg, nos infectados. Na mesma ordem também diminuiram o colesterol livre de 539 ñ 80, para 396 ñ 54 microng/mg; os ésteres do colesterol de 270 ñ 35, para 216 ñ 36 microng/mg e os colinafosfatídios de 44 ñ 5,7 para 31 ñ 4,9 microng/mg. Os serinafosfatídios, os etanolaminafosfatídios e os esfingofosfatídios aumentaram, respectivamente de 58 ñ 9,7 para 60 ñ 8,5, de 72 ñ 7,8 para 111 ñ 15,7 e de 36 ñ 4,9 para 63 7,1 microng/mg. Os ácidos graxos livres näo se alteram significativamente, passaram de 1,7 ñ 0,35 micronEq/g, nos controles, para 1,8 ñ 0,29 micronEq/g nos animais infectados. Esses resultados padecem indicar que na fase inicial de esquistossomose mansônica hepática, antes da formaçäo dos granulomas, säo detectadas alteraçöes importantes na constituiçäo lipídica das membranas do compartimento lisossônico. Elas, talvez, sejam devidas a produtos catabólicos, excretados por vermes imaturos ou adultos, presentes em vasos do sistema portal

Bioquímica da esquistossomose mansônica: VI - Alteraçöes do compartimento lisossômico hepático relacionadas ao tempo de infecçäo / Biochemistry of Schistosomiasis mansoni: VI - Alterations of hepatic lysosomes behavior relative to the infection period

O Schistosoma mansoni e/ou seus ovos causam uma hepatopatia muito importante e com aspectos anátomo-clínicos bam característicos. Uma vez carregados pela corrente circulatória, os vermes podem ocluir ramos dicotômicos de maior calibre do sistema portal e, quando mortos produzem lesöes às vezes extensas, primeiro necróticas, depois inflamatórias e, posteriormente cicatriciais, sempre circunscritas e näo sistematizadas. Os ovos, além de penetrarem nos ramúsculos näo dicotômicos da rede periductal alcançam os ramos de distribuiçäo ou até mesmo as vênulas aferentes, ocluindo muitas delas e, como conseqüência, formam os granulomas intravasculares que podem levar a uma interrupçäo da corrente sangüínea portal a esse nível e alteraçöes da circulaçäo intralobular. A diminuiçäo da taxa de oxigênio disponível e conseqüêntemente o decréscimo do pH intra e extracelular säo potentes labilizadores das membranas dos diversos componentes do compartimento lisossônico. A saída de hidrolases ácidas, proteínas catiônicas e hidrolases neutras, a partir desses orgânulos, acarreta agressöes tissulares muito importantes, com o desencadeamento e/ou manutençäo dos processos inflamatórios típicos desta parasitose. Neste trabalho estudou-se as atividades lisossômicas ligadas às diversas fases da esquistossomose mansônica hepática. Os resultados indicaram que a integridade funcional dos complexos membranosos do compartimento lisossômico foi significativamente alterada, já a partir do segundo mês da infecçäo e que parece haver um estreito relacionamento entre o agravamento das lesöes inflamatórias hepáticas com uma maior labilidade lisossômica