RESUMO
Nematode infections induce the upregulation of mucin- and glycosylation-related genes in intestinal epithelial cells in vivo. However, the factor(s) that induce these changes in epithelial cells have not been fully elucidated. In the present study, we analysed the effects of the Th2 cytokines IL-4 and IL-13 and the excretory-secretory (ES) product of the nematode Nippostrongylus brasiliensis on the gene expression of the major mucin core peptide MUC2, the sialyltransferase ST3GalIV (Siat4c) and the sulphotransferase HS3ST1 in intestinal epithelium-derived IEC-6 cells by quantitative reverse transcription (RT)-PCR. The administration of IL-4 and IL-13 resulted in a significant upregulation of ST3GalIV and HS3ST1 gene transcription, but had no effect on MUC2, in IEC-6 cells. RT-PCR studies also demonstrated the constitutive expression of IL-13Ralpha1 and IL-4R in IEC-6 cells. On the other hand, the ES product induced upregulation of ST3GalIV, but not HS3ST1 or MUC2, while coadministration of IL-13 and the ES product induced a slight but significant upregulation of MUC2. Co-incubation of live N. brasiliensis adult worms with IEC-6 cells resulted in the upregulation of ST3GalIV and MUC2. These results suggested that HS3ST1 gene expression is strictly regulated by IL-4/IL-13, while ST3GalIV and MUC2 gene expressions are regulated by redundant mechanisms.
Assuntos
Íleo/parasitologia , Interleucina-13/fisiologia , Interleucina-4/fisiologia , Mucina-2/biossíntese , Nippostrongylus/patogenicidade , Sialiltransferases/biossíntese , Sulfotransferases/biossíntese , Animais , Antígenos de Helmintos/fisiologia , Células Epiteliais/imunologia , Células Epiteliais/parasitologia , Perfilação da Expressão Gênica , Íleo/imunologia , Masculino , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , beta-Galactosídeo alfa-2,3-SialiltransferaseRESUMO
Previous studies have shown that host immunity regulates the fecundity of nematodes. The present study was aimed at clarifying the reversible nature of fecundity in response to changes of immunological status and to determine which effector cells are responsible for compromising fecundity in Heligmosomoides polygyrus. Enhanced fecundity was observed in immunocompromised SCID and nu/nu mice compared to those in the corresponding wild-type mice, with significantly fewer numbers of intrauterine eggs produced in the wild-type than in the immunodeficient mice. When 14-day-old adult worms from BALB/c mice were transplanted into naïve BALB/c mice, their fecundity increased significantly as early as 24 h post-transplantation, but not when they were transferred into immune mice, suggesting the plastic and reversible nature of fecundity in response to changes in host immunological status. In mast cell-deficient W/W(v) mice, nematode fecundity was significantly higher than in mast cell-reconstituted W/W(v) or +/+ mice. The serum levels of the mast-cell protease mMCP1 were markedly increased in the wild-type as well as the mast cell-reconstituted W/W(v), but not in the W/W(v), SCID, or nu/nu mice during infection. These findings raise the interesting possibility that certain activities of mast cells, either directly or indirectly, regulate parasite fecundity during infection.
Assuntos
Fertilidade/imunologia , Mastócitos/imunologia , Nematospiroides dubius/imunologia , Infecções por Strongylida/imunologia , Animais , Quimiocina CCL2/sangue , Fezes/parasitologia , Feminino , Masculino , Mastócitos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos SCID , Nematospiroides dubius/citologia , Contagem de Ovos de Parasitas , Organismos Livres de Patógenos EspecíficosRESUMO
To determine the role of T cells and mast cells in intestinal pathology and immune expulsion of intestinal nematodes, worm burdens, goblet cell responses and villus structures were analysed in T- and B-cell-deficient severe combined immunodeficiency (SCID) mice, athymic nu/nu mice and mast cell deficient W/W(v) mice after infection with the nematode Heligmosomoides polygyrus. SCID and nu/nu mice showed significantly higher worm burdens at week 9 post-infection compared with the wild-type controls. SCID and nu/nu mice showed compromised goblet cell hyperplasia and/or Muc 2 expression, indicating that both events are T-cell dependant. On the other hand, the SCID mice showed increased pathology (villus atrophy and crypt hyperplasia) and increased numbers of proliferating cell nuclear antigen positive cells compared to the wild-type controls. W/W(v) mice, conversely, were able to expel the worms normally, had normal goblet cell hyperplasia, and did not demonstrate the changes in mucosal architecture seen in SCID mice, confirming that a normal mast cell response is not necessarily required for these changes. These results suggest that a functional T-cell response, but not a mast cell response, is necessary for anti-parasite responses, goblet cell function, and maintaining normal mucosal architecture.
Assuntos
Células Caliciformes/imunologia , Nematospiroides dubius , Infecções por Strongylida/imunologia , Infecções por Strongylida/patologia , Animais , Atrofia/patologia , Contagem de Células , Hiperplasia/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Nus , Camundongos SCID , Mucina-2/metabolismoAssuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antiparasitários/uso terapêutico , Foliculite/tratamento farmacológico , Ivermectina/uso terapêutico , Infestações por Ácaros/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Adulto , Humanos , Masculino , Medição de RiscoRESUMO
We encountered four patients with overt primary sclerosing cholangitis (PSC) which were histologically classified into stage 2 or 3. We examined the expression of stem cell factor (SCF), a ligand of c-kit, in injured bile ducts by immunohistochemistry, and mast cells were identified by immunohistochemistry using anti-HMCT (human mast cell tryptase) and anti-c-kit antibodies to clarify their relation with portal fibrosis coincident with destroyed bile ducts. SCF was detected in the epithelia of most bile ducts in PSC, and many HMCT- and c-kit-positive mast cells were found in portal tracts. Image analysis showed more significant numbers of c-kit-positive mast cells per area of portal tract in PSC than in chronic hepatitis C, and they might increase from stage 2 to 3. c-Kit-positive cells infiltrated into the portal tracts with SCF-positive destroyed bile ducts, and c-kit mast cells should be investigated in detail to make a role for portal fibrosis in PSC.
RESUMO
To determine whether common helminth infections could modify the intestinal immunopathological status of the host, the expression in the human duodenal mucosa of cytokines, eosinophil- and mast-cell-specific molecules and monosaccharide transporters of the glucose-transporter (GLUT) family was explored. The 31 subjects were all patients at the gastro-intestinal disease unit of Nongkhai Hospital, Thailand. Four of the 10 patients who presented with eosinophilia (> or = 6.0% of their leucocytes were eosinophils), and five of the other 21 patients, had intestinal infections with helminths when they presented or within the previous 3 months. Studies based on semi-quantitative, reverse-transcriptase PCR revealed that the interleukin-5/interferon-gamma ratio was significantly higher in the noneosinophilic, helminth-infected patients than in the non-eosinophilic, uninfected patients, whereas the IgE receptor type I (Fc epsilon RI)/mast-cell tryptase ratio was significantly higher in the eosinophilic, helminth-infected patients than in the eosinophilic, uninfected patients. Expression of Charcot-Leyden-crystal protein, GLUT-1 and GLUT-5, however, showed no significant inter-group differences. Principal-components analysis of the data on eosinophils, interleukin-5, interferon-gamma, Fc epsilon RI and mast-cell tryptase revealed that one principal component could discriminate the patients who had helminth infection from the non-eosinophilic, uninfected patients, but not from the eosinophilic, uninfected patients. These results indicate that, whatever the intestinal pathology, patients infected with common intestinal helminths tend to develop a mucosal immunological response of the Th2 type.
Assuntos
Helmintíase/imunologia , Enteropatias Parasitárias/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Adulto , Citocinas/análise , Citocinas/imunologia , Duodeno/imunologia , Duodeno/parasitologia , Eosinofilia/imunologia , Eosinofilia/parasitologia , Eosinófilos/imunologia , Eosinófilos/parasitologia , Feminino , Transportador de Glucose Tipo 1 , Transportador de Glucose Tipo 5 , Glicoproteínas/análise , Helmintíase/parasitologia , Humanos , Interferon gama/análise , Interleucina-5/análise , Enteropatias Parasitárias/parasitologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/parasitologia , Lisofosfolipase , Masculino , Mastócitos/imunologia , Mastócitos/parasitologia , Pessoa de Meia-Idade , Proteínas de Transporte de Monossacarídeos/análise , Proteínas de Transporte de Monossacarídeos/imunologia , Receptores de IgE/análise , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologiaRESUMO
BACKGROUND: Small intestinal epithelial cells (IEC) show apoptosis in physiological turnover of cells and in certain inflammatory diseases. AIMS: To investigate the role of caspases in the progression of IEC apoptosis in vivo. METHODS: IEC were separated along the villus-crypt axis from the jejunum of normal and Nippostrongylus brasiliensis infected rats at 4 degrees C. Caspases were examined by a fluorometric assay method, histochemistry, and immunoblotting. RESULTS: Villus cell rich IEC from normal rats exhibited a high level of caspase-3-like activity whereas activities of caspase-1, -8, and -9 were negligible. Immunoblotting analysis of villus cell rich IEC revealed partial cleavage of procaspase-3 into a 17 kDa molecule as well as cleavage of a caspase-3 substrate, poly(ADP-ribose) polymerase (PARP), whereas in crypt cell rich IEC, caspase-3 cleavage was less significant. Caspase-3 activity was also observed histochemically in villus epithelium on frozen sections of the normal small intestine. IEC prepared at 4 degrees C did not reveal nuclear degradation whereas subsequent incubation in a suspension at 37 degrees C induced intense nuclear degradation within one hour in accordance with increases in active caspase-3. This apoptosis was partially suppressed by the caspase inhibitor Z-VAD-fmk. Nematode infected animals showed villus atrophy together with significant increases in levels of caspase-3 in IEC but not of caspase-1, -8, or -9. CONCLUSION: Caspase-3 may have an important role in the physiological replacement of IEC as well as in progression of IEC apoptosis induced by nematode infection.
Assuntos
Caspases/fisiologia , Células Epiteliais/enzimologia , Intestino Delgado/enzimologia , Nippostrongylus , Infecções por Strongylida/enzimologia , Animais , Apoptose/fisiologia , Western Blotting , Bromodesoxiuridina/metabolismo , Células Cultivadas , Eletroforese em Gel de Ágar , Ativação Enzimática , Ensaio de Imunoadsorção Enzimática , Fluorimunoensaio/métodos , Intestino Delgado/citologia , Masculino , Microscopia de Fluorescência , Ratos , Ratos Endogâmicos BNRESUMO
Protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, modulates smooth muscle tone and exocrine secretion in the salivary glands and pancreas. Given that PAR-2 is expressed throughout the gastrointestinal tract, we investigated effects of PAR-2 agonists on mucus secretion and gastric mucosal injury in the rat. PAR-2-activating peptides triggered secretion of mucus in the stomach, but not in the duodenum. This mucus secretion was abolished by pretreatment with capsaicin, which stimulates and ablates specific sensory neurons, but it was resistant to cyclo-oxygenase inhibition. In contrast, capsaicin treatment failed to block PAR-2-mediated secretion from the salivary glands. Intravenous calcitonin gene-related peptide (CGRP) and neurokinin A markedly elicited gastric mucus secretion, as did substance P to a lesser extent. Specific antagonists of the CGRP1 and NK2, but not the NK1, receptors inhibited PAR-2-mediated mucus secretion. Pretreatment with the PAR-2 agonist strongly prevented gastric injury caused by HCl-ethanol or indomethacin. Thus, PAR-2 activation triggers the cytoprotective secretion of gastric mucus by stimulating the release of CGRP and tachykinins from sensory neurons. In contrast, the PAR-2-mediated salivary exocrine secretion appears to be independent of capsaicin-sensitive sensory neurons.
Assuntos
Duodeno/efeitos dos fármacos , Mucinas Gástricas/metabolismo , Oligopeptídeos/farmacologia , Peptídeos , Receptores de Trombina/metabolismo , Estômago/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Capsaicina/farmacologia , Diclofenaco/farmacologia , Duodeno/metabolismo , Duodeno/fisiologia , Mucinas Gástricas/efeitos dos fármacos , Masculino , Misoprostol/farmacologia , Neurocinina A/farmacologia , Inibidores de Proteases/farmacologia , Ratos , Ratos Wistar , Receptor PAR-2 , Receptores de Trombina/agonistas , Receptores de Trombina/genética , Saliva/química , Estômago/patologia , Estômago/fisiologia , Substância P/farmacologiaRESUMO
Infections with helminthic parasites occasionally induce pulmonary diseases with possible involvement of immunological mechanisms. In rats infected with the nematode Nippostrongylus brasiliensis, pulmonary granulomatous lesions develop and persist after the larvae have migrated through the lungs. To determine the pathogenesis of this lesion, we examined cytokine gene expression in the lungs using RT-PCR and in situ hybridization. Two weeks after infection, when fully developed lesions appeared, levels of IL-3 and of type2 cytokines IL-4, IL-5, IL-6 and IL-13 gene expression were markedly enhanced in whole lung homogenates. Those of IL-2 and IFN-gamma were also slightly increased 2 weeks postinfection. IL-12 mRNA level did not change after 2 weeks but was slightly increased after 4 weeks. Levels of IL-10 and proinflammatory cytokine TNF gene expression did not show significant changes, although a slight increase was observed in IL-1beta message after 2 weeks. In situ hybridization studies showed that lung granulomatous lesions were composed mainly of lymphoid cells expressing IL-3, IL-4 and IL-13 mRNA, but not IFN-gamma mRNA. IL-5 mRNA-expressing cells were fewer in number than these cells. RMCP II immunohistochemistry revealed that mast cells increased in number in the lung granulomas. From these results, it was concluded that the nematode infection-associated lung granuloma was a type 2 lesion.
Assuntos
Citocinas/genética , Pneumopatias Parasitárias/imunologia , Pulmão/imunologia , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Células Th2/imunologia , Animais , Modelos Animais de Doenças , Expressão Gênica , Pulmão/patologia , Pneumopatias Parasitárias/genética , Pneumopatias Parasitárias/patologia , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos BN , Infecções por Strongylida/genética , Infecções por Strongylida/patologiaRESUMO
Cadherins, calcium-dependent cell adhesion molecules, play crucial roles, not only in the maintenance of tissue integrity, but also in the regulation of many aspects of cell behavior. We investigated the expression of "classic" E-, N- and P-cadherins in bone marrow-derived cultured mast cells (BMMC) and peritoneal mast cells (PMC) from mice. Flow cytometric analysis and immunocytochemical staining indicated that E-cadherin was expressed on the cell surface of BMMC and also at lower levels on PMC. N-cadherin was also expressed on the surface of BMMC, but not of PMC, whereas P-cadherin expression was seen in neither cell type. Significant expression of E- and N-cadherin mRNA was observed in BMMC by reverse transcriptase-polymerase chain reaction (RT-PCR), but PMC expressed only E-cadherin mRNA. Western blotting analysis indicated expression of alpha- and beta-catenins and p120-catenin (or p120 cas) in BMMC, whereas PMC showed less intense expression of alpha- and beta-catenins with high levels of p120 expression. Analyses of beta-catenin or E-cadherin immunoprecipitates from BMMC lysate revealed that alpha-catenin, beta-catenin, and E-cadherin were co-precipitated, suggesting that E-cadherin and catenins form a complex in mast cells. Addition of a blocking antibody of homophilic E-cadherin interactions, or a synthetic E-cadherin-binding decapeptide containing the histidine-alanine-valine (HAV) sequence in methylcellulose cultures of gut intraepithelial mononuclear cells or BMMC, significantly suppressed the clonal growth of mast cells. Furthermore, the blocking antibody or synthetic decapeptide significantly suppressed BMMC adhesion to E-cadherin-expressing F9 cell monolayers. These results indicated that E-cadherin and associated cytoplasmic proteins in mast cells might be involved in the regulation of certain stages of mast cell differentiation and cell-cell interactions.
Assuntos
Caderinas/análise , Moléculas de Adesão Celular/análise , Proteínas do Citoesqueleto/análise , Mastócitos/química , Fosfoproteínas/análise , Transativadores , Animais , Cateninas , Adesão Celular , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Mastócitos/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Ratos , alfa Catenina , beta Catenina , delta CateninaRESUMO
Although certain helminth infections preferentially induce type 2 T-cell responses, the immunological mechanisms responsible for type 2 T-cell polarization remain unclear. In the present study, we investigated the effects of excretory-secretory (ES) antigen from the nematode Nippostrongylus brasiliensis on cytokine production by mesenteric lymph node (MLN) cells isolated from naive rats. MLN cells produced considerable levels of gamma interferon (IFN-gamma) during a 72-h stimulation with concanavalin A (ConA) or with immobilized anti-CD3 plus soluble anti-CD28 antibodies (anti-CD3/CD28). With either stimulation, 10 microg of ES antigen per ml significantly suppressed IFN-gamma and interleukin-2 (IL-2) production without cytotoxic activity. The copresence of anti-IL-4, anti-IL-10, or transforming growth factor beta (TGF-beta) blocking antibodies did not alter the suppressive effect of ES antigen on IFN-gamma production. ES antigen did not affect IL-10 production. Kinetic studies of the effect of ES antigen indicated that the antigen suppressed even ongoing IFN-gamma production. Reverse transcription-PCR study showed that in the presence of ES antigen, IFN-gamma mRNA expression by MLN cells was suppressed 6 and 12 h after ConA or anti-CD3/CD28 stimulation. ES antigen also significantly suppressed IFN-gamma production by purified CD4(+) or CD8(+) T cells during anti-CD3/CD28 stimulation but did not affect IL-4 production by CD4(+) T cells. These findings suggested that the nematode antigen suppressed production of IFN-gamma and IL-2 but not IL-4 or IL-10 production. ES antigen-mediated suppression of IFN-gamma during the initiation of the immune response may provide a microenvironment that helps generation of type 2 T cells.
Assuntos
Antígenos de Helmintos/imunologia , Interferon gama/biossíntese , Ativação Linfocitária , Nippostrongylus/imunologia , Linfócitos T/imunologia , Transcrição Gênica , Animais , Linfócitos T CD8-Positivos/imunologia , Interferon gama/genética , Interleucina-10/biossíntese , Interleucina-4/biossíntese , Interleucina-4/genética , Linfonodos/imunologia , Masculino , Ratos , Ratos Endogâmicos F344RESUMO
While investigating the effect of marine products on cell growth, we found that visceral extracts of Chub mackerel, an ocean fish, had a powerful and dose-dependent apoptosis-inducing effect on a variety of mammalian tumor cells. This activity was strikingly dependent on infection of the C. mackerel with the larval nematode, Anisakis simplex. After purification of the protein responsible for the apoptosis-inducing activity, we cloned the corresponding gene and found it to be a flavoprotein. This protein, termed apoptosis-inducing protein (AIP), was also found to possess an endoplasmic reticulum retention signal (C-terminal KDEL sequence) and H2O2-producing activity, indicating that we had isolated a novel reticuloplasimin with potent apoptosis-inducing activity. AIP was induced in fish only after infection with larval nematode and was localized to capsules that formed around larvae to prevent their migration to host tissues. Our results suggest that AIP may function to impede nematode infection.
Assuntos
Anisaquíase/imunologia , Anisakis/imunologia , Apoptose/imunologia , Peixes/imunologia , Flavoproteínas/genética , Flavoproteínas/isolamento & purificação , Proteínas de Membrana/genética , Proteínas de Membrana/isolamento & purificação , Células 3T3 , Sequência de Aminoácidos , Animais , Anisaquíase/parasitologia , Anisakis/genética , Anisakis/metabolismo , Anisakis/patogenicidade , Fator de Indução de Apoptose , Cálcio/metabolismo , Clonagem Molecular , Retículo Endoplasmático/fisiologia , Fibrinolisina/fisiologia , Peixes/parasitologia , Flavoproteínas/imunologia , Flavoproteínas/metabolismo , Células HL-60 , Humanos , Peróxido de Hidrogênio/metabolismo , Larva/genética , Larva/imunologia , Larva/metabolismo , Larva/patogenicidade , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Camundongos , Dados de Sequência MolecularRESUMO
Autoinfective strongyloidiasis is potentially fatal, yet the majority of infected individuals harbour asymptomatic and chronic infections. The role of humoral responses in modulating autoinfection was assessed by examining antibody isotype responses to filariform larval antigens amongst chronically infected ex-Far East Prisoners of War (exFEPOWs) with longstanding (> 30 years) infection. Serum immunoglobulin (Ig)G1, IgG4, IgE and IgA responses to whole Strongyloides stercoralis L3 extracts and their constituent antigenic components were characterized by ELISA and quantitative immunoblotting. Comparison of two groups of S. stercoralis infected exFEPOWs with and without detectable larvae in stool demonstrated novel trends. Significantly enhanced recognition of six immunodominant antigenic components by IgA was associated with undetectable larval output, as was enhanced IgE recognition of several components. Additionally, IgE and IgG4 exhibited parallel antigen recognition patterns. These findings are consistent with roles for IgA in modulating larval output, for IgE in regulating autoinfection, and for IgG4 in blocking IgE-mediated responses in human strongyloidiasis.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Citocinas/genética , Nippostrongylus , Infecções por Strongylida/imunologia , Actinas/genética , Animais , Linfonodos/metabolismo , Masculino , Mesentério , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos F344RESUMO
To determine the role of mast cells in the recruitment of neutrophils and eosinophils, acute nonspecific pleurisy was induced by injecting isologous serum into normal +/+ and mast cell-deficient Ws/Ws rats. In +/+ rats, neutrophil infiltration peaked 4 h after serum administration, followed by influx of eosinophils after 24-48 h. The levels of neutrophil influx after 4 h as well as the activity of myeloperoxidase (MPO) in pleural lavage-cell extract were significantly lower in Ws/Ws rats than in +/+ rats. In contrast, numbers of eosinophils as well as activity of eosinophil peroxidase (EPO) did not differ significantly between Ws/Ws and +/+ rats. For local reconstitution of mast cells, +/+ rat peritoneal mast cells (PMC) or mesenteric lymph node cells (MLNC) as a control were transferred into the Ws/ Ws pleural cavity. Serum injection into animals with PMC transfer 7 days previously triggered augmented neutrophil influx by approximately 4.7-fold as compared to that in MLNC-transferred animals. Mast cells recovered from the pleural cavity of PMC-transferred rats showed histamine contents equivalent to 20% of that of freshly isolated PMC and retained the reactivity to compound 48/80. These results indicated that dependency of neutrophil recruitment on resident mast cells is greater than that of eosinophils in isologous serum-induced pleurisy.
Assuntos
Quimiotaxia de Leucócito , Síndromes de Imunodeficiência/imunologia , Mastócitos/fisiologia , Pleurisia/imunologia , Animais , Líquido da Lavagem Broncoalveolar , Transplante de Células , Peroxidase de Eosinófilo , Eosinófilos/enzimologia , Eosinófilos/imunologia , Feminino , Liberação de Histamina , Síndromes de Imunodeficiência/genética , Linfonodos/citologia , Masculino , Mastócitos/enzimologia , Mastócitos/transplante , Neutrófilos/enzimologia , Neutrófilos/imunologia , Peroxidase/análise , Peroxidases/análise , Pleura , Proteínas Proto-Oncogênicas c-kit/genética , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos , Ratos MutantesRESUMO
It has been reported that infection with Nippostrongylus brasiliensis induces villus atrophy with various histological alterations. In N. brasiliensis-infected rats, villus length in the jejunum was reduced significantly at day 10 p.i., when serum levels of rat mast cell protease (RMCP) II had increased significantly. To determine whether the villus atrophy is associated with enhancement of apoptosis, apoptotic nuclei were labelled using the nick end-labelling method. Numbers of labelled cells were markedly increased in the villus epithelium at 7-10 days p.i., while the numbers returned to normal 14 days p.i. when worms were rejected from the intestine and villus length became normal. Examination of the expression of the adhesion molecule E-cadherin showed granular immunoreactivity in the cytoplasm of atrophic villus epithelium with loss of normal localization to epithelial cell borders. In mast cell-deficient Ws/Ws rats, villus length was reduced as significantly as in +/+ counterparts at day 10 p.i. with marked increases in the numbers of apoptotic cells. These results suggested that villus atrophy was closely associated with enhanced apoptosis and loss of adhesion in epithelial cells. Mast cell activation appears not to be involved in these alterations.
Assuntos
Apoptose , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Nippostrongylus/parasitologia , Infecções por Strongylida/patologia , Animais , Atrofia , Caderinas/isolamento & purificação , Adesão Celular , Quimases , Grânulos Citoplasmáticos , Mucosa Intestinal/parasitologia , Intestino Delgado/parasitologia , Masculino , Mastócitos/enzimologia , Antígeno Nuclear de Célula em Proliferação/isolamento & purificação , Proteínas Proto-Oncogênicas c-kit/genética , Ratos , Ratos Mutantes , Serina Endopeptidases/sangue , Infecções por Strongylida/parasitologiaRESUMO
A 38-year-old Japanese male who had traveled in China from September 13 to October 5, 1997, developed fever and severe conjunctivitis from October 20. After he was hospitalized in Kyoto City Hospital for persistent high fever on October 29, he developed muscular weakness and dysphagia which continued for two weeks. An electromyogram showed a myogenic pattern, and laboratory findings showed significant elevation of serum enzyme levels of muscle origin: CPK, 3,095 IU/l; aldorase, 195 IU/l; myoglobin, 7,570 ng/ml, and myoglobinuria, 94,700 ng/ml. The WBC was 10,800/microliter with 45% eosinophils. Muscular biopsy showed degeneration of muscle fibers with infiltration of macrophages and lymphocytes. On further inquiry, it was revealed that the patient had eaten smoked bear meat in China on September 30, three weeks prior to the onset of symptoms. A dot-ELISA serologic test for parasites was positive for Trichinella. Further, a coiled 1.2 mm long Trichinella larve was recovered from approximately 100 mg of frozen biopsied muscle by an enzyme digestion method. Mebendazole was given to the patient at a dosage of 200 mg/day for seven days. CPK levels were normalized within 3 days of the beginning of the treatment, and he was discharged without any symptoms. Physicians must be aware of trichinellosis and should include it in their differential diagnosis when examining patients with myositis and eosinophilia of unknown origin.
Assuntos
Miosite/etiologia , Triquinelose/complicações , Adulto , China , Humanos , Masculino , ViagemRESUMO
Ws/Ws rats are deficient in both mucosal- and connective tissue-type mast cells. To study the role of mast cells in active anaphylaxis, changes in vascular permeability in the trachea upon intravenous antigen challenge with Evans blue dye were examined in Ws/Ws, heterogenic Ws/+, and normal +/ + rats sensitized with the nematode Nippostrongylus brasiliensis. Antigen challenge resulted in fatal anaphylactic shock in some +/+ and Ws/+ rats, but not in Ws/Ws rats. Marked dye leakage developed within 30 min in the trachea of +/+ and Ws/+ rats, while Ws/Ws rats showed no substantial increases in the levels of vascular permeability. Ex vivo stimulation of sensitized lung fragments from +/+ animals with specific antigen induced significant releases of histamine and leukotriene (LT) C4, while sensitized Ws/Ws rat-lung fragments did not. In Ws/Ws rats, levels of nematode-specific IgE, IgG1 and IgG2a antibodies as well as levels of lung eosinophilia were not significantly different from those in +/+ rats. These results show that mast cell-deficient Ws/Ws rats fail to develop active anaphylaxis, and this is mediated probably by the lack of mast cell-derived mediators required for initiation of the reaction.
Assuntos
Anafilaxia/imunologia , Anafilaxia/parasitologia , Pulmão/imunologia , Pulmão/parasitologia , Mastócitos/imunologia , Mastócitos/parasitologia , Nippostrongylus/imunologia , Animais , Anticorpos Anti-Helmínticos/biossíntese , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Permeabilidade Capilar , Contagem de Células , Liberação de Histamina , Imunização , Leucotrieno C4/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Mastócitos/patologia , Ratos , Ratos Mutantes , Infecções por Strongylida/imunologia , Infecções por Strongylida/metabolismo , Infecções por Strongylida/patologia , Traqueia/irrigação sanguíneaRESUMO
The effects of lactic dehydrogenase virus (LDV) infection on the protective immune responses to the nematode Nippostrongylus brasiliensis were studied. Mice with chronic LDV infection showed significantly higher levels of parasite egg production than non-LDV-infected (control) mice after N. brasiliensis infection. Concurrent LDV infection also suppressed peripheral blood eosinophilia and the lung mastocytosis induced by this nematode. LDV infection showed higher expression levels of the interferon-gamma (IFN-gamma) mRNA in lymph nodes compared with control mice before N. brasiliensis infection. In addition, the IgG2a production in LDV-infected mice was higher than that in control mice before and after N. brasiliensis infection. These results suggest that LDV infection modulates protective immune responses against N. brasiliensis infection by the activation of T-helper type 1 cells.
Assuntos
Infecções por Arterivirus/imunologia , Vírus Elevador do Lactato Desidrogenase , Nippostrongylus , Infecções por Strongylida/imunologia , Animais , Infecções por Arterivirus/parasitologia , Doença Crônica , Eosinófilos/imunologia , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Interferon gama/biossíntese , Jejuno/imunologia , Contagem de Leucócitos , Pulmão/imunologia , Linfonodos/imunologia , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Contagem de Ovos de Parasitas , RNA Mensageiro/metabolismo , Infecções por Strongylida/parasitologiaRESUMO
A 53-year-old male acromegalic patient with advanced rectal adenocarcinoma developed pleuritis in the course of cobalt irradiation, steroid treatment and chemotherapy. Examination of drained pleural fluid demonstrated numerous motile organisms, which were identified as Trichomonas tenax by Giemsa staining. Peptostreptococcus micros was also detected in the cultures of pleural fluid and blood. Treatment with metronidazole successfully eliminated the protozoa and cured the pyothorax.
Assuntos
Adenocarcinoma/complicações , Empiema Pleural/etiologia , Hospedeiro Imunocomprometido , Neoplasias Retais/complicações , Tricomoníase/etiologia , Acromegalia/complicações , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Animais , Antitricômonas/uso terapêutico , Neoplasias da Medula Óssea/secundário , Neoplasias Encefálicas/secundário , Empiema Pleural/tratamento farmacológico , Humanos , Neoplasias Hepáticas/secundário , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Trichomonas/isolamento & purificação , Tricomoníase/tratamento farmacológicoRESUMO
The time-course of differentiation/proliferation of mast cells in gut epithelium was investigated in mice infected with the nematode Strongyloides venezuelensis. After infection, expression of proliferating cell nuclear antigen increased in gut intraepithelial mast cells on days 7 to 11, followed by an increase in the number of intraepithelial mast cells from days 11 to 14. Mast cell precursors were defined as cells that formed mast cell colonies in methylcellulose culture. After infection, the numbers of mast cell precursors in the population of gut intraepithelial mononuclear cells (IEMNC) increased significantly on day 3 and returned to the pre-infection level by day 7. Mast cell precursors in Peyer's patches, mesenteric lymph nodes (MLN), and spleen also increased from day 7 p.i. Production of IL-3 and IL-4 in MLN and spleen were increased between 7 and 11 days p.i. These results show that murine intestinal mastocytosis is initiated by an early increase in mast cell precursor number in the gut epithelium followed by proliferation/differentiation of mast cells. Mast cell precursor numbers increased even before the production of IL-3 and IL-4 in MLN and spleen, suggesting that some local factors might be involved in this phenomenon.