RESUMEN
By using IL-5 transgenic mice, it has been shown that eosinophils might play a key role in elimination of larval stages of nematode infections. The present study was carried out to clarify molecular mechanisms involved in the eosinophil-mediated killing of Nippostrongylus brasiliensis larvae. The larvicidal activity was observed in the presence of normal serum in vitro. Electron microscopic observations revealed firm attachment of eosinophils to the cuticular surface of larvae, which was damaged by electron-dense materials released from eosinophils. The larvicidal activity was abrogated by heat- or zymosan-treatment of the serum, whereas depletion of IgG or IgM from the serum did not interfere with eosinophil adhesion and killing. Moreover, pretreatment of eosinophils with monoclonal antibodies against CD11b or VLA-4 inhibited the eosinophil-mediated killing of larvae. Immunofluorescent staining demonstrated the deposition of C3c and plasma fibronectin on the cuticle of the larvae. These results indicate that interactions between CD11b and VLA-4 and their respective counter-ligands deposited on the cuticle are essential in eosinophil-mediated adhesion and damage to larvae of N. brasiliensis.
Asunto(s)
Proteínas del Sistema Complemento/fisiología , Eosinófilos/inmunología , Fibronectinas/metabolismo , Nippostrongylus/inmunología , Infecciones por Strongylida/inmunología , Animales , Adhesión Celular , Integrina alfa4beta1 , Integrinas/metabolismo , Interleucina-5/genética , Larva/inmunología , Antígeno de Macrófago-1/metabolismo , Ratones , Ratones Endogámicos C3H , Ratones Transgénicos , Nippostrongylus/crecimiento & desarrollo , Receptores Mensajeros de Linfocitos/metabolismo , Infecciones por Strongylida/parasitologíaRESUMEN
OBJECTIVE: To observe the anti-P. berghei ability of C57BL/6 mice after infected with Nippostrongylus brasiliensis alterations in T helper cell subsets in the course of Plasmodium infection, and the effect of the alteration on host's prognoses. METHODS: C57BL/6 mice were infected with Nippostrongylus brasiliensis subcutaneously, 3 wk later, the mice were injected with Plasmodium berghei intraperitoneally. The parasitemia was monitored daily. On days 0, 3 and 9, RNA from the spleens of infected mice was prepared for PT-PCR to analyse the changes of IFN-gamma and IL-4 mRNA during the infection course. RESULTS: Compared with control group, the peak-reaching time of parasitemia in the experiment group was delayed, and the bearing capacity of mice to malaria infection and the surviving time increased obviously. The IL-4 level in the experiment group was higher than that in the control group on day 0 of P. berghei infection, but all raised abnormally in both groups at the early stage of the infection; while IFN-gamma level in the experiment group was higher than that in the control group on day 3 after infection, and then began to reduce to some extent on day 9 of the infection in the experiment group. CONCLUSION: T helper cell subsets play an important role in antimalarial immunoregulation in mice.
Asunto(s)
Malaria/inmunología , Nippostrongylus/inmunología , Plasmodium berghei/inmunología , Infecciones por Strongylida/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Malaria/parasitología , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Eosinophil and IgE responses of interleukin (IL)-5 transgenic and normal C3H/HeN mice were studied after experimental infection with Nippostrongylus brasiliensis (Nb). Intestinal worms were recovered at day 5 post-infection (PI), and numbers of total white blood cells (WBC) and eosinophils, and total serum IgE and anti-hapten (dinitrophenyl) (DNP) specific IgE titers, were measured at days 0, 14 and 21 PI. IL-5 mice appeared resistant to Nb infection showing a significantly lower worm recovery rate than normal mice (P < 0.05). Total WBC and eosinophil counts (/mm3) were significantly increased in Nb infected normal mice (P < 0.05), but unchanged (total WBC) or decreased (eosinophils) in IL-5 mice at day 21 PI. The total serum IgE level remarkably increased in normal mice, but only a little in IL-5 mice at days 14 and 21 PI. Priming with DNP brought about more remarkable increases of the total and anti-DNP specific IgE in normal mice than in IL-5 mice. The results show that IL-5 mice are resistant to Nb infection, and that eosinophil and IgE responses in these mice are not augmented by Nb infection.
Asunto(s)
Anticuerpos Antihelmínticos/sangre , Eosinófilos/inmunología , Inmunoglobulina E/sangre , Interleucina-5/genética , Nippostrongylus , Infecciones por Strongylida/inmunología , Animales , Femenino , Recuento de Leucocitos , Ratones , Ratones Endogámicos C3H , Ratones Transgénicos/inmunología , Nippostrongylus/inmunologíaRESUMEN
Nippostrongylus brasiliensis infection is characterized by blood and tissue eosinophilia induced by interleukin (IL)-5 secreted from CD4+ T cells. However, it is still obscure whether eosinophils play an important role in the protection against N. brasiliensis infection. In this study we attempted to determine whether the in vivo environment of IL-5 transgenic mice, characterized by high eosinophil production, could affect the worm burden after N. brasiliensis infection. Kinetic studies on the infection demonstrated a significantly lower worm recovery from the intestine of IL-5 transgenic mice compared to age-matched background controls. This tendency was also observed at the lung stage of the infection. Furthermore, with respect to elevation of the serum IgE concentration, the peak level was observed at 2 weeks after infection in infected background control mice with four times higher concentrations than those of uninfected mice. In contrast, the increase of IgE concentration in IL-5 transgenic mice was very limited and low. The adoptive transfer of eosinophils from IL-5 transgenic mice into background control animals resulted in the reduction of worm recovery from the lungs, suggesting that eosinophils play a key role in the protection against migrating larvae of N. brasiliensis. These results indicate that the innate high level of eosinophils due to constitutive production of IL-5 augments immunity against N. brasiliensis infection.
Asunto(s)
Eosinófilos/inmunología , Interleucina-5/inmunología , Nippostrongylus/inmunología , Infecciones por Strongylida/inmunología , Traslado Adoptivo , Animales , Anticuerpos Antihelmínticos/sangre , Movimiento Celular , Eosinofilia/inmunología , Eosinófilos/citología , Eosinófilos/trasplante , Inmunoglobulina E/sangre , Interleucina-5/genética , Larva/inmunología , Recuento de Leucocitos , Pulmón/parasitología , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Transgénicos , Células Th2/inmunologíaRESUMEN
OBJECTIVE: To determine age-adjusted reference intervals for children for serum granulocyte colony-stimulating factor (G-CSF) levels. DESIGN: We determined the serum G-CSF levels of 168 disease-free children who were term neonates to 15 years of age with a highly sensitive chemiluminescent enzyme immunoassay. RESULTS: The lowest values (5 ng/L) exceeded the detectable limit (1 ng/L) of this assay technique. The G-CSF levels were highest on the day of birth (mean +/- SD 147 +/- 146 ng/L); thereafter values decreased to 46 +/- 33 ng/L in the early neonatal period and to 23 +/- 10 ng/L in the late neonatal period. The G-CSF levels both on the day of birth and in the early neonatal period were significantly higher than in all older age groups. No significant differences were found among any of the age groups after 4 weeks of age. The G-CSF values were correlated with both blood leukocyte counts (r = 0.496, p < 0.0001) and neutrophil counts (r = 0.547, p < 0.0001). In children older than 4 weeks of age (n = 128), the 95% reference interval for G-CSF values was 5 to 42 ng/L. CONCLUSIONS: Our study in disease-free children revealed that change in serum G-CSF levels are age dependent and are correlated with neutrophil counts. Determination of reference intervals for the neonatal period requires further study.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Recuento de Leucocitos , Mediciones Luminiscentes , Masculino , Neutrófilos , Valores de Referencia , Estudios RetrospectivosRESUMEN
To clarify whether administration of recombinant human erythropoietin (rHuEpo) may have toxic effects on neutrophil production in premature infants, 10 low birth weight infants who received rHuEpo, 200 U/kg per week, were studied retrospectively. Treated infants were compared with 10 untreated infants. None of the infants studied had infection antenatally or postnatally. In both groups the neutrophil count remained greater than 5000/mm3 for the first 3 weeks and decreased markedly at approximately 4 weeks. Although reticulocyte counts were significantly elevated in the rHuEpo-treated group, the difference in neutrophil counts between the groups was not significant. In addition, administration of rHuEpo did not exert any significant effect on granulocyte-macrophage colony formation of circulating hematopoietic progenitors in neonates. Thus no evidence was found that administration of rHuEpo has toxic effects on granulopoiesis in premature infants.
Asunto(s)
Eritropoyetina/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Recien Nacido Prematuro/sangre , Neutrófilos/efectos de los fármacos , Proteínas Recombinantes/farmacología , Eritropoyetina/administración & dosificación , Sangre Fetal/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Granulocitos/efectos de los fármacos , Humanos , Recién Nacido de Bajo Peso/sangre , Recién Nacido , Recien Nacido Prematuro/inmunología , Recuento de Leucocitos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Proteínas Recombinantes/administración & dosificación , Estudios RetrospectivosRESUMEN
We have been able to produce a mouse monoclonal IgE antibody specific to an adult worm antigen extracted from Schistosoma japonicum (Sj). The antibody was able to elicit passive cutaneous anaphylaxis in the rat skin against Sj with the highest titer of 1:256,000 but did not cross-react with S. mansoni antigen. The antibody recognized a 97-kDa molecule expressed on the surface of mechanically transformed schistosoma of S. japonicum. Passive transfer of the antibody into mice in the early stage of challenge infection resulted in a partial but significant reduction of recovery of adult worms. Induction of eosinophilia by an oral administration of embryonated eggs of Toxocara canis prior to challenge infection enhanced the reduction.
Asunto(s)
Anticuerpos Antihelmínticos/inmunología , Anticuerpos Monoclonales/inmunología , Inmunoglobulina E/inmunología , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/prevención & control , Animales , Anticuerpos Antihelmínticos/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Eosinofilia/complicaciones , Inmunización Pasiva , Inmunoglobulina E/administración & dosificación , Ratones , Anafilaxis Cutánea Pasiva , Ratas , Toxocariasis/complicacionesRESUMEN
To obtain direct evidence for the involvement of IgE antibodies in eosinophil-mediated killing of schistosomula of S. japonicum, dinitrophenylated (DNP) schistosomula pretreated with mouse monoclonal IgE antibodies were co-cultured with purified rat peritoneal eosinophils. It was found that the eosinophil-mediated adherence and damage to haptenated schistosomula were dependent on a monoclonal anti-DNP IgE antibody, but not on monoclonal anti-ovalbumin IgE antibody. Moreover, eosinophils from N. brasiliensis-infected rats demonstrated an enhanced ability in the IgE-dependent damage to DNP-schistosomula as compared with the cells from normal rats. The enhancement was associated with an increase in the proportion of eosinophils expressing Fc receptors for IgE.
Asunto(s)
Anticuerpos Monoclonales/fisiología , Citotoxicidad Inmunológica , Eosinófilos/inmunología , Inmunoglobulina E/fisiología , Infecciones por Nematodos/inmunología , Receptores Fc/análisis , Esquistosomiasis/inmunología , Animales , Adhesión Celular , Dinitrobencenos/inmunología , Eosinófilos/metabolismo , Eosinófilos/fisiología , Haptenos/inmunología , Inmunoglobulina E/metabolismo , Ratones , Nippostrongylus/inmunología , Ratas , Ratas Endogámicas , Receptores de IgE , Formación de Roseta , Schistosoma japonicum/inmunología , Esquistosomiasis/parasitologíaRESUMEN
A new antiallergic agent, 4-(p-chlorobenzyl)-2-[N-methyl-perhydroazepinyl-(4)]-1-(2H)-phthalazinone hydrochloride (azelastine), was found to exert inhibitory effects on passive cutaneous anaphylaxis in the rat and on expulsion of Nippostrongylus brasiliensis from the rat intestine when this agent was administered intravenously at appropriate doses.
Asunto(s)
Antagonistas de los Receptores Histamínicos H1/farmacología , Infecciones por Nematodos/inmunología , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Ftalazinas/farmacología , Piridazinas/farmacología , Animales , Clemastina/farmacología , Relación Dosis-Respuesta a Droga , Inmunoglobulina E/farmacología , Masculino , Nippostrongylus , RatasRESUMEN
Nippostrongylus brasiliensis infection was found to be highly effective in inducing a carrier-specific enhancing effect on primary and secondary antihapten IgE antibody response in the rat, when animals were immunized i.p. with 10 mug of dinitrophenylated N. brasiliensis protein (DNP-Nb) plus 10 mg Al(OH)3 2 weeks after the infection. The carrier effect by the infection was much greater than that obtained by any other supplementary immunization with the carrier (Nb) plus adjuvant, so far examined, in terms of the IgE antibody response. The results, together with our previous observation in the mouse, provide an explanation for the reason why antiworm IgE antibodies are so easily detectable in helminth infections.