Trypanosoma cruzi infection in mice enhances the membrane expression of low-affinity Fc receptors for IgG and the release of their soluble forms

The membrane expression of low-affinity Fc receptors for IgG (FcγRII/III) on cells and the number of FcγRII/III(+) cells were studied by flow cytometry, using the 2-4G2 MoAb, in mice infected by Trypanosoma cruzi. Cells from spleen, mesenteric lymph nodes and peritoneum were collected on days 10, 20, 30 and 40 post infection (p.i.). The in vivo serum level of soluble FcγRII/III, as well as its in vitro release by cells from infected mice were studied. Parasitaemia and IgG1, IgG2a and IgG2b T. cruzi-specific antibody titres were also recorded. Both the expression of FcγR on cell membrane and the absolute number of FcγR(+) cells increased in spleen and in mesenteric lymph nodes, but not in peritoneum. The modifications in spleen occurred in the early and late parasitaemic phase of infection, i.e., before and after detection of T. cruzi-specific antibodies (from day 10 to 40 p.i.). In mesenteric lymph nodes, the variations were observed only in the early acute infection, when antibodies were not yet detectable at significant levels (on days 10 and 20 p.i.). Higher levels of soluble FcγR were detected in sera and in culture supernatants of spleen and lymph node cells from day 20 to 40 p.i. These results show that T. cruzi infection in mice upregulates the expression and the release of FcγRII/III, in the acute phase of infection, before as well as after the rise of antibody response.     

Maturation of the rat small intestine at weaning: changes in epithelial cell kinetics, bacterial flora, and mucosal immune activity.

The relationship between maturation of the small intestine and change in mucosal immune activity was examined in the DA rat during the weaning period from 12 to 30 days. Two stages of jejunal maturation were observed: an initial stage of morphological development and crypt proliferation (days 12 to 22), followed by a period of stabilisation (days 24 to 30). By day 22 of the initial phase, villi increased principally in width but not in length, crypt length increased, and crypt cell production rate increased from 0.5 (day 12) to 11.1 (day 22) cells/crypt/hour. Various measures of mucosal immune activity showed a biphasic response. Up to days 20 to 22, the weight of the mesenteric lymph node increased seven-fold (p less than 0.0001), counts of jejunal eosinophils and goblet cells increased 3- (p less than 0.0001) and 19-fold (p less than 0.0001) respectively, and mean serum rat mucosal mast cell protease II, released from mucosal mast cells, increased from 24 (day 12) to 313 (day 22) ng/ml (p less than 0.0001). After day 22, mesenteric lymph node weight stabilised, eosinophil count stabilised and goblet cells decreased, serum rat mucosal mast cell protease II decreased three-fold (p less than 0.0001), and mean jejunal count of intraepithelial lymphocytes increased from 26 (day 22) to 54 (day 24) cells per mm of muscularis mucosae (p less than 0.0001), before stabilising. These results demonstrated a close association between maturation of the small intestine and change in activity of the mucosal immune system.     

Effects of granulocyte-colony stimulating factor on peritoneal defense mechanisms and bacterial translocation after administration of systemic chemotherapy in rats

AIM: To investigate the effects of granulocyte-colony stimulating factor (G-CSF) on peritoneal defense mechanisms and bacterial translocation after systemic 5-Fluorouracil (5-FU) administration. METHODS: Thirty Wistar albino rats were divided into three groups; the control, 5-FU and 5-FU + G-CSF groups. We measured bactericidal activity of the peritoneal fluid, phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, total peritoneal cell counts and cell types of peritoneal washing fluid. Bacterial translocation was quantified by mesenteric lymph node, liver and spleen tissue cultures. RESULTS: Systemic 5-FU reduced total peritoneal cell counts, neutrophils and macrophage numbers. It also altered bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. 5-FU also caused significant increase in frequencies of bacterial translocation at the liver and mesenteric lymph nodes. G-CSF decreased bacterial translocation, it significantly enhanced bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. It also increased total peritoneal cell counts, neutrophils and macrophage numbers. CONCLUSION: Systemic 5-FU administration caused bacterial translocation, decreased the bactericidalactivity of peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. G-CSF increased both bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, and prevented the bacterial translocation. We conclude that intraperitoneal GCSF administration protects the effects of systemic 5-FU on peritoneal defense mechanisms.     

Mitogenic Effect of Syngeneic Peritoneal Fluids and their Relation to Lymphocyte Trapping

Abstract. Syngeneic peritoneal fluids, i.e. tumor ascitic fluid (TAF); peritoneal exudate fluid (PEF) or normal peritoneal washouts, induce a mitogenic effect in the spleens and lymph nodes of syngeneic animals. Fractions of TAF and PEF of MW less than 1,000 are also effective mitogenic stimulators. The mesenteric lymph nodes, thymus and nonlymphoid tissues, i.e. lung, kidney and liver, are not stimulated. The mitogenic effect peaks at day 3 with a second minor peak at day 7 and disappears by day 9. The mitogenic effect is unrelated to the ability of TAF and PEF to abrogate lymphocyte trapping.     

Antibody-forming potential of lymph nodes in aged mice, with special reference to the influence of adjuvant.

The secondary antibody-forming potential of non-splenic lymphatic tissues during senescence was investigated in NMRI/Han mice, both at the cellular and humoral levels. The mean life span of conventionally reared NMRI/Han mice amounts to 19.86 months. After primary immunization of aged (20-month-old) NMRI mice with 4 X 10(8) sheep erythrocytes (SE) by the intraperitoneal (i.p.) route, the primary antibody-forming potential of both spleen and lymph nodes was significantly reduced, as compared to young adult (3-month-old) controls. In contrast, the anamnestic response elicited by an i.p. booster injection of 4 X 10(8) SE at the 44th day after primary immunization was not significantly diminished in comparison to the controls. When killed cells of Bordetella pertussis were found to be significantly increased in young adult as well as in aged mice. These data obtained at the cellular level were in accordance with corresponding serological findings. The impressive restitution of the antibody-forming potential evident after secondary antigenic stimulation was associated with a remarkable restitution of the lymph node morphology. This was particularly pronounced in the pronounced in the parathymic lymph nodes which represent the draining nodes for the peritoneal cavity. These findings indicate that the lymph nodes of the senescent individual also possess remarkable reserves in immunocompetence.     

Trichinella spiralis: Intestinal expression of systemic stage-specific immunity to newborn larvae

Rats immunized with newborn Trichinella spiralis larvae i.v. were found to confer a specific anti-newborn larvae immunity in the small intestine. In rats immunized with newborn larvae i.v. and then challenged with adult worms intraintestinally, total newborn larvae recovery was reduced by 75-90% in thoracic duct lymph and in hepatic portal vein blood. No newborn larvae were found in the peritoneal fluid of immunized rats. In addition to an absolute reduction in number, larval migration from the small intestine to the thoracic duct was delayed by 6-12 h and migration to the portal vein was inhibited for at least 8 h. The establishment of adult worms in the small intestine and female worm fecundity were not affected by anti-newborn larvae immunity. Identical quantitative effects on newborn larvae migration from the small intestine were achieved by homologous transfer of anti-newborn larvae immune serum i.v. into naive recipient rats.     

Prolonged effects of nitrogen mustard on mouse haematopoietic and lymphoid tissues.

Groups of mice have been autopsied at regular intervals during the period of lymphomyeloid tissue regeneration which follows the phase of hypocellularity induced by the i.v. injection of 100 mug (4 mg/kg bodyweight) nitrogen mustard. The marrow cellularity recovered to levels in the normal range by the 8th day and remained in this range up to the 40th day. Subsequently, the marrow showed a slight degree of hypocellularity up to day 120. Granulocytes were predominant during the initial phase of marrow regeneration during the second week post-injection. The thymus exhibited periodic size variations such that it was substantially larger than the thymus of age-matched controls from 20-30 d, 46-73 d, and 75-100 d after injection. The lymph nodes and lymphoid tissue of the spleen regenerated only slowly to reach control values by 40-50 d. Superimposed on the recovering lymphoid tissue of the spleen was a phase of erythroid hyperplasia lasting from 10-18 d post-injection. This coincided with a shift from granulocytosis to erythroid hyperplasia in the marrow. This erythroid hyperplasia lasted until day 30 when the cellular composition of the marrow and spleen returned to normal. A possible explanation of these results is that nitrogen mustard introduces a degree of synchrony into stem cell proliferation and differentiation. Additionally, these results emphasize the role of the haematopoietic microenvironment in the control of stem cell differentiation.     

High concentration of bilirubin in post-nodal lymph associated with red blood cell catabolism in lymph nodes of the sheep.

Qualitative and quantitative analysis of post-nodal lymph of the sheep has shown that the distinct yellow colour of this fluid pool is due to the presence of relatively large amounts of bilirubin. In efferent lymph from thepopliteal, prefemoral, prescapular, renal and intestinal lymph nodes total bilirubin concentrations were 3-8 times higher than the corresponding concentrations in blood plasma. In contrast the total bilirubin concentrations in afferent lymph from the lower leg and kidney were less than the corresponding concentrations in blood plasma. Histological examination of several popliteal and mesenteric lymph nodes revealed the presence of free iron and bilirubin in the cytoplasm of cells located near the lymphatic sinuses of the node. In addition, the concentration of bilirubin in efferent lymph from the popliteal node was observed to increase following an induced rise in the number of red blood cells reaching the node by way of the afferent lymphatic duct. These latter observations suggest that the bilirubin in post-nodal lymph is associated with the catabolism of extravascular red cells by reticulo-endothelial cells within the lymph nodes.     

Prolonged Effects of Nitrogen Mustard on Mouse Haematopoietic and Lymphoid Tissues

Groups of mice have been autopsied at regular intervals during the period of lymphomyeloid tissue regeneration which follows the phase of hypocellularity induced by the i.v. injection of 100 μg (4 mg/kg bodyweight) nitrogen mustard. The marrow cellularity recovered to levels in the normal range by the 8th day and remained in this range up to the 40th day. Subsequently, the marrow showed a slight degree of hypocellularity up to day 120. Granulocytes were predominant during the initial phase of marrow regeneration from days 5–12. The thymus, lymph nodes, and spleen commenced regeneration during the second week post-injection. The thymus exhibited periodic size variations such that it was substantially larger than the thymus of age-matched controls from 20–30 d, 46–73 d, and 75–100 d after injection. The lymph nodes and lymphoid tissue of the spleen regenerated only slowly to reach control values by 40–50 d. Superimposed on the recovering lymphoid tissue of the spleen was a phase of erythroid hyperplasia lasting from 10–18 d post-injection. This coincided with a shift from granulocytosis to erythroid hyperplasia in the marrow. This erythroid hyperplasia lasted until day 30 when the cellular composition of the marrow and spleen returned to normal. A possible explanation of these results is that nitrogen mustard introduces a degree of synchrony into stem cell proliferation and differentiation. Additionally, these results emphasize the role of the haematopoietic microenvironment in the control of stem cell differentiation.     

Role of the digestive tract immune system in the control of bacterial translocation in gnotoxenic mice

The aim of this work was to study the role of gut associated lymphoid tissue in the control of bacterial translocation. Two strains of Escherichia coli were orally inoculated to 71 axenic mice. Ten days after, the 2 initial strains and 2 others, resulting from plasmidic exchanges, were present in the digestive tract of the mice which were divided in two groups: the first group (n = 41) received one intraperitoneal injection of cyclophosphamide 100 mg/kg; the second control group (n = 30) received isotonic saline. The following parameters were studied 3, 5 and 9 days after the injection: the population level of the 4 strains in the caecum, their translocation to mesenteric lymph nodes, liver, spleen and circulating blood, the density per unit surface of lamina propria plasma cells and intraepithelial lymphocytes in duodenal and caecal mucosae. The population in each strain found in the caecum was different from the 3 others but similar within the two groups of animals and remained unchanged with time. In the control group, bacterial translocation to the mesenteric lymph nodes decreased (p less than 0.01), while the density of plasma cells increased (p less than 0.01) from the 3rd to the 9th days. In the cyclophosphamide treated group, translocation to the mesenteric lymph nodes increased (p less than 0.01), while the density of intestinal plasma cells decreased (p less than 0.05) from the 3rd to the 9th days. Density of intraepithelial lymphocytes did not vary with time in each group and from one group to another. Bacterial translocation to liver, spleen and systemic blood was weak and did not increase in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on antigenspecific immunosuppression: Influence of 6-mercaptopurine-BGG-conjugates on BGG binding cells (author's transl)]

The rosette forming cell (RFC) response of different lymphoid organs (spleen, lymph node, peripheral blood) of guinea pigs was examined by immunocytoadherence. The method has been adapted to work with the soluble antigen BGG. The number of antigen binding cells following immunization with BGG in CFA reached the highest level on day 6 in Ln. popliteus and on the 10th day in spleen and peripheral blood. It is shown that the highest level of antigen binding cells appears generally before the maximum of circulating antibodies. After i.p.-immunization to alum-adsorbed BGG we only detected a small number of RFCs. After pretreatment with 6-mercaptopurineI-25-BGG (MP-BGG) and a control substance (toluylI-25-BGG) over 8 days and in increasing doses we obtained an antigenspecific suppression of BGG binding cells following MP-BGG treatment. In contrast to these findings the antibody titres were only slightly decreased in the beginning of the immune response.     

Molecular mechanism about lymphogenous metastasis of hepatocarcinoma cells in mice

AIM: To investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor cells in lymph nodes. METHODS: Fifty-six inbred 615-mice were equally divided into 2 groups and inoculated with Hca-F and Hca-P cells. Their lymph node metastatic rates were examined. Growth fraction of lymphocytes in host lymph nodes was detected by flow cytometry. The Hca-F and Hca-P cells were cultured with extract of lymph node, liver or spleen. The quantity of MMPs in these supernatants was examined by zymographic analysis. The expression of Fas ligand, PCNA, Bcl-2 protein of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry. The apoptosis signals of macro-phages in lymph nodes were observed with in situ DNA fragmentation. RESULTS: On the 28th day post-inoculation, the lymph node metastatic rate of HcaF was 80%(16/20), whereas that of Hca-P was 25%(5/20). The growth fraction of lymphocytes was as follows: in the Hca-F cells, the proliferating peak of lymphocytes appeared on the 14th day post inoculation and then decreased rapidly, while in HcaP cells, the peak appeared on the 7th day post inoculation and then kept at a high level. With the extract of lymph node, the quantity of the MMP-9 activity increased (P<0.01) and active MMP-9 and MMP-2 were produced by both Hca-F and Hca-P tumor cells, which did not produce MMPs without the extract of lymph node or with the extracts of the liver and spleen. The expression of Fas Ligand of Hca-F cells was stronger than that of Hca-P cells (P <0.01). The expressions of PCNA and Bcl-2 protein of Hca-F cells in the tumors of inoculated area were the same as that of Hca-P cells. In situ DNA fragmentation showed that the positive signals of macrophages were around Hca-F cells. CONCLUSION: Secretion of MMPs which was associated with metastatic ability of Hca-F and Hca-P tumor cells depends on the environment of lymph nodes. The increased expression of Fas ligand protein of Hca-F tumor cells with high lymphogenous metastatic potential in lymph nodes may help tumor cells escape from being killed by host lymphocytes.     

Mononuclear phagocytes: a major population of effector cells responsible for rejection of allografted tumor cells in mice.

To understand the in situ mechanism of immunological response of recipient animals to allografted tumor cells, the types of cells that infiltrated into the rejection site were examined. When Meth A cells (H-2d) were given i.p. to an allogeneic [C57BL/6 (H-2b)] strain of mouse, the tumor cells ceased to grow on the 6th day, accompanied by an i.p. infiltration of leukocytes. The tumor cells were totally eliminated from the peritoneal cavity around the 12th day. The highest cytotoxic activity against Meth A cells was obtained with the peritoneal exudate cells harvested on day 8. On this day, the exudate cells consisted of three populations when examined by flow cytometry, and each was isolated by sorting. Each of them appeared to be homogeneous, and they were morphologically identified as lymphocytes; granulocytes; and medium-sized, mononuclear, less-granular cells. The cytotoxic activity was confined exclusively to the last population. The effector cells (H-2b) were cytotoxic against not only Meth A cells (H-2d) but also concanavalin A-stimulated allogeneic spleen cells [C3H/He (H-2k), CBA/N (H-2k), A/J (H-2a), BALB/c (H-2d), and DBA/2 (H-2d) strains of mouse]. The effector cells were totally inert against concanavalin A-activated syngeneic spleen cells [C57BL/6 (H-2b) and C57BL/10 (H-2b) strains of mouse]. The effector cells were phenotypically (Thy-1.2- CD3- Lyt-1- Lyt-2- L3T4- immunoglobulin- asialo GM1-), morphologically, and functionally distinct from cytotoxic T cells, natural killer cells, and lymphokine-activated killer cells but were adherent mononuclear phagocytes.     

Endogenous RNA tumor viruses are activated during chemical induction of murine plasmacytomas.

Plasmacytomas are induced in BALB/c mice by the intraperitoneal injection of pristane (2,6,10,14-tetra-methylpentadecane) after a latent period of six months and more [Anderson, P. N. & Potter, M. (1969) Nature 222, 994-995]. Spleen cells mesenteric lymph node cells, thoracic lymph node cells, and peritoneal exudate cells were prepared from pristane-treated and control uninjected BALB/c mice during the course of a 10-month period, and these cell suspensions were tested for the release of infectious murine leukemia viruses. Endogenous ecotropic and xenotropic murine leukemia viruses were expressed in pristane-treated mice during the latter part of the tumor induction period, in those cell populations in which transformed plasma cells appear, namely, peritoneal exudate cells and thoracic lymph node cells. The significance of preferential expression of both ecotropic and xenotropic murine leukemia virus in target cell populations following the administration of a carcinogen is discussed in terms of the possible formation of an oncogenic variant virus.     

周期型马来丝虫实验感染小白鼠体内发育和病理观察

目的 观查周期型马亚丝虫在小白鼠体内发育和病理变化。方法 生只鼠腹腔内注射从东乡伊蚊收集６０－２００条感染期幼虫，定期抽查微丝蚴并解剖观察病理变化。结果 在感染泊３０－３１０天解剖分别检获Ⅳ期，幼虫，童虫和成虫，成虫阳性率为３４．６２％（９／２６），主要病变为淋巴管炎、淋巴结炎，及其周围炎，在肺、脾、睾丸和精索可见淋巴栓塞，含有成虫和炎细胞，肺部可见退行性变的成虫和幼虫，形成丝虫性肉芽肿性病变。结     

Temporal clinical,proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis

AIM To investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium(DSS)-induced acute colitis.METHODS Acute colitis was induced in C57 BL/6 female mice by administration of 1%, 2% or 3% DSS in drinking water for 7 d. Animals were monitored daily for weight loss, stool consistency and blood in the stool, while spleens and colons were harvested on day 8. A time course analysis was performed in mice ingesting 3% DSS, which included colon proteomics through multiplex assay, colon histological scoring by a blinded investigator, and immune response through flow cytometry or immunohistochemistry of the spleen, mesenteric lymph node and colon.RESULTS Progressive worsening of clinical colitis was observed with increasing DSS from 1% to 3%. In mice ingesting 3% DSS, colon shortening and increase in proinflammatory factors starting at day 3 was observed, with increased spleen weights at day 6 and day 8. This coincided with cellular infiltration in the colon from day 2 to day 8, with progressive accumulation of macrophages F4/80~+, T helper CD4~+(Th), T cytotoxic CD8~+(Tcyt) and T regulatory CD25~+(Treg) cells, and progressive changes in colonic pathology including destruction of crypts, loss of goblet cells and depletion of the epithelial barrier. Starting on day 4, mesenteric lymph node and/or spleen presented with lower levels of Treg, Th and Tcyt cells, suggesting an immune cell tropism to the gut. CONCLUSION These results demonstrate that the severity of experimental colitis is dependent on DSS concentration, correlated with clinical, proteomic, histological and cellular immune response on 3% DSS.     

Bacterial translocation in cirrhotic rats. Its role in the development of spontaneous bacterial peritonitis.

Bacterial translocation occurs in ascitic cirrhotic rats, but its association with ascites infection is unknown. The aim of this study was to assess the relation between bacterial translocation and ascites infection in cirrhotic rats. Male Sprague-Dawley rats were induced to cirrhosis with intragastric CCl4. Ascitic fluid, portal and peripheral blood, mesenteric lymph nodes, liver and spleen samples were cultured before death in those cirrhotic rats with less (group A) or more (group B) than 250 polymorphonuclear neutrophils/mm3 in ascitic fluid, as well as in healthy control rats. Histological examination of jejunum, ileum, and caecum was also performed. Bacterial translocation occurred in 45% of ascitic rats (without differences between groups A and B), but in 0% controls (p = 0.01). Bacterial translocation was associated with positive ascitic fluid culture in 60% of the cases. In all of them the same bacterial species was isolated in both mesenteric lymph node and ascitic fluid. Submucosal caecal oedema (100%), ileal lymphangiectasia (41%), and caecal inflammatory infiltrate (41%) occurred in ascitic rats, the last being associated with ascitic fluid positive culture (p = 0.04). These results suggests that bacterial translocation occurs frequently in ascitic cirrhotic rats, and may play a permissive, but not unique, part in a number of ascites infections. Whether histological changes seen in cirrhotic ascitic rats favour bacterial translocation remains to be elucidated.     

Fasciola hepatica: rapid switching of stage-specific antigen expression after infection

Early developmental stages of the trematode parasite Fasciola hepatica were collected from the peritoneal cavity and liver of mice during a ten day infection period. Using one dimensional SDS-PAGE, differences in protein expression profiles were observed in stages collected on the same day post-infection in different physiological locations and also in juvenile parasites collected from the same location on different days post-infection. Four rat monoclonal antibodies were raised against the parasite using lymph nodes draining infected tissues. Three monoclonal antibodies, FY3-1, FY3-2 and FY4-7, were generated using cells from the mesenteric lymph node of recently challenged immune rats, while FY1-6 was derived from hepatic lymph node cells of a chronically infected rat. The epitope recognized by FY3-2 appeared to be carbohydrate in nature and was present on the surface of newly excysted juveniles. Immunoblots revealed that the antigens recognized by FY3-1, FY3-2 and FY4-7 were only expressed for two days after infection. In contrast, FY1-6 recognized epitopes expressed across all developmental stages screened. The rapid changes in protein and antigen expression observed during the early stages of infection may assist the parasite to evade the host immune response.     

Angio-immunoblastic lymphadenopathy with fibrosis of bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph nodes

We report a 47-year-old man diagnosed as angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) with fibrosis of the bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph node. He was admitted to a hospital in May, 1980 because of general fatigue, cough, fever and systemic lymphadenopathy. The diagnosis of AILD was based on a biopsy of right cervical lymph node. His symptoms were improved but recurred with the addition of icterus and progressive pancytopenia with decrement of prednisolone. He was referred to our hospital in July, 1980 and his physical examination revealed generalized lymphadenopathy, icterus and hepatosplenomegaly. Hemogram showed pancytopenia, and needle biopsy of the bone marrow disclosed fibrosis. Sections from the lymph node showed AILD with proliferation of epithelioid cells. Administration of 60 mg/day of prednisolone improved the fever, lymphadenopathy and hepatosplenomegaly. However he died suddenly of acute respiratory failure on July 30. Autopsy showed fibrosis of bone marrow, lymph node, liver and spleen with infiltration of abnormal lymphocytes, and pulmonary aspergillosis.     

Anti-inflammatory responses and oxidative stress in Nippostrongylus brasiliensis-induced pulmonary inflammation

Migration of L3 larvae of Nippostrongylus brasiliensis through the lungs of the rat, during primary infection, was studied at 24 h, 72 h and 8 days. At 24 h p.i., there was evidence of damage to lung epithelial cells and microvasculature, with increased protein and gamma-glutamyl transpeptidase in the bronchoalveolar lavage (BAL) fluid. However, there was little evidence of inflammatory cell recruitment. At 24 h p.i., there was a significant reduction in the inflammatory cytokine tumour necrosis factor alpha. Superoxide (O2-*) production was also reduced, accompanied by an increase in superoxide dismutase activity. Lipid peroxidation was reduced at 24 h p.i. and L3 larvae were shown to possess high levels of glutathione compared to host lung tissue. Nitric oxide, detected as nitrite, was produced in BAL fluid, and inducible nitric oxide synthase protein was increased by 72 h p.i. There was evidence of peroxynitrite production throughout the infection period with specific protein bands nitrosylated at 75, 30 and 25 kDa. It appears that despite early evidence of lung damage, the inflammation was reduced in response to L3 larvae of N. brasiliensis.