Serum immunoglobulin levels in nude mice

A quantitative evaluation of Ig classes in the serum of “nude” mice(nu/nu) in comparison with nu/+ and +/+ animals is reported. IgA and IgG classes are shown to be reduced in “nude” mice, the reduction being particularly severe in the case of IgG₁. On the other hand these animals have normal IgM levels.     

Nephrotoxic nephritis in nude mice.

We investigated the role of T cells in the pathogenesis of murine nephrotoxic nephritis (NTN). The disease was produced by injecting congenitally athymic nude (nu/nu) mice and their normal heterozygous (nu/+) littermates with rabbit anti-rat glomerular basement membrane (GBM) antiserum. Within 2-4 weeks we noted marked thrombotic lesions and depositions of mouse IgG, IgM, C3 and rabbit IgG along the GBM in both groups of mice. There was no significant difference in the extent of glomerular involvement between the two groups of mice. We conclude that T cell immunodeficiency plays no role in the development of severe glomerular lesions in murine NTN.     

Tissue histamine levels in male and female normal and nude mice

In comparison with those in normal (+/+) mice, tissue histamine levels were lower in athymic (nu/nu) female mice and higher in athymic male mice. The sexual difference was less marked or absent in nu/nu mice. These results show (a) that endocrine factors are involved in the distribution of tissue histamine, and (b) that the thymus cannot be considered as the main source of tissue histamine in pathogen-free mice.     

Serum IgE levels in liver cirrhosis.

Abstract. Hypergammaglobulinemia is a well-known feature of liver cirrhosis, but studies on serum IgE in this setting are limited. The present study evaluates serum IgE concentration in a group of cirrhotic patients and examines their relationship with aetiological, clinical and analytical parameters (including liver function tests and hepatic phagocytic activity). The presence of specific IgE against common dietary antigens was also investigated. Total serum IgE was determined by enzyme immunoassay (EIA) in 52 cirrhotics (27 alcoholic and 25 non-alcoholic, including eight virus B and seven virus C-related cirrhosis, three primary biliary cirrhosis, three cryptogenic, three haemochromatosis and one Wilson's disease) and 34 healthy subjects (used as controls). Serum IgE (1U/ml) in contols was not significantly different from that of cirrhotic patients (median 42, range 2–726 vs median 86, range 2-> 1000, respectively) (P=NS). However, serum IgE among alcoholics (median 199, range 19- < 1000) was higher than that of controls (P < 0-001), virus B-related cirrhotics (median 25, range 3-< 1000) (P < 0-05), virus C-related cirrhotics (median 47, range 2-170) (P < 0-05), or nonalcoholic cirrhotics as a whole (median 23, range 2-< 1000) (P < 0.01). High IgE levels (≥ 170 1U/ml) were detected in 55.5% of alcoholics compared with only 12% of nonalcoholic cirrhotics (P < 0.01). Moreover, IgE levels were very high (> 1000 1U/ml) in six patients of the alcoholic group (22.2%) compared with only one non-alcoholic patient (4%). Increased serum IgE levels did not seem to be related to either parameters of liver function (serum bilirubin, albumin, prothrombin or Child-Pugh score), hepatic phagocytic function or other immunoglobulins. Skin-prick tests failed to demonstrate increased sensitization to eight common dietary antigens in the patients studied. On multivariate analysis, only the alcoholic aetiology of the disease correlated with high serum IgE levels. These data suggest that increased serum IgE might be a common and rather specific feature of chronic alcoholic liver disease.     

Histoplasma capsulatum infection in nude mice.

Congenitally athymic nude (nu/nu) mice, when injected intraperitoneally with Histoplasma capsulatum, developed a rapidly fatal disseminated infection characterized by heavy parasitization of reticuloendothelial tissues. In contrast, their heterozygous (nu/X) littermates, which possessed a functioning thymus, developed only a low-grade infection which was apparently self-limited and rarely fatal. Transplantation of thymic tissue into nu/nu mice diminished greatly the severity of infection and reduced mortality by about 50%. These studies emphasize the importance of cell-mediated immunity in host defense against histoplasmosis and suggest that the nude mouse may be a valuable model for the study of this chronic intracellular infection.     

Modulation of total IgE levels in serum of normal and athymic nude BALB/c mice by T cells and exogenous antigenic stimulation

Several different grades of T-system impairment were studied for their effects on the total serum IgE concentration in BALB/c mice. Homozygous athymic nu/nu mice and their heterozygous nu/+ littermates were compared for serum IgE levels while kept under either barrier-maintained or conventional conditions. The results show a paradox between the T-cell dependency of the IgE immune response and the increased levels of serum IgE in the absence of T cells. Both barrier-maintained and conventionalized nu/nu mice have at least twofold increased serum IgE levels as compared to nu/+ mice. With age, IgE levels increased faster and reached higher plateau values in nu/nu than nu/+ mice. Moreover, after adult thymectomy of BALB/c mice the serum IgE levels increased up to 15-fold at 4 months of age, while infusion of immunocompetent T cells in nude mice resulted in a 2- to 5-fold decrease of the IgE level.     

Interferon production in athymic nude mice.

Athymic (homozygous nude) mice of a non-inbred stock had relatively little antiviral activity in their serum compared with normal control mice at 4, 6 and 6.5 h after the intraperitoneal injection of Newcastle disease virus. The antiviral activity in the serum had the characteristics of interferon. At 10 h after injection and thereafter, the serum titres were comparable in nude and normal control mice. Exceptional nude mice with thymus-like tissue sometimes produced interferon more or less normally. Transfer of spleen cells from normal donor mice, but not from nude donors, led to increased serum interferon levels in nude recipient mice at 4 h after virus injection.     

Listeria monocytogenes infection in nude mice.

As compared to phenotypically normal (nu/+)NMRI mice showing the typical course of an experimental listeric infection, that of congenitally hypothymic (nude, nu/nu)NMRI mice was found to be characterized from the outset bya chronic trend. During the early phase of the infection, significantly reduced numbers of Listeria monocytogenes were observed in the spleens of nude mice.     

Viral infections and IgE levels.

Six non-atopic patients with respiratory infections to a variety of viruses demonstrated a consistent drop in IgE levels (35% to 87%) in the convalescent phase compared to the acute phase of infection, suggesting that the viral agent affects T lymphocytes to suppress and hence B lymphocytes to secrete IgE immunoglobulin.     

荷人鼻咽癌裸鼠血内皮抑素的水平变化

目的:探讨不同病期荷人鼻咽癌裸鼠血内皮抑素水平的变化,及其与肿瘤发展的关系。方法:采用BALB/C裸小鼠复制荷人鼻咽癌裸鼠模型,通过EIA方法测定不同病期荷人鼻咽癌裸鼠血内皮抑素的浓度,称取瘤重。结果:荷瘤鼠血中内皮抑素含量在种瘤5d组[(137.61±53.41)μg/L]或10d组[(103.06±17.33)μg/L]与正常裸鼠[(113.56±21.74)μg/L]比较未见明显差异(P>0.05),而种瘤20d组、30d组、40d组[(212.80±85.91)μg/L、(293.63±62.53)μg/L、(271.57±32.45)μg/L]显著高于正常裸鼠(P<0.05)。随着荷瘤时间的延长,瘤宿主血内皮抑素含量逐渐升高,种瘤20d组明显增高,并持续维持在高水平。瘤重与血中内皮抑素含量呈正相关关系(r=0.687)。结论:提示肿瘤的发展与血内皮抑素含量的变化可能有关。     

Effects of anti-epsilon on total and specific IgE levels in adult mice

Adult (2- to 3-month-old) female CBA/J mice were injected intraperitoneally with heavy chain specific rabbit anti-IgE (anti-epsilon) to determine its effects on total and specific serum IgE. Animals receiving 10 X 250 micrograms injections over a 50-day period displayed significantly increased (10 X levels of serum IgE compared to rabbit gamma-globulin or untreated controls. If animals were immunized with castor allergen (CA) prior to anti-epsilon treatments their IgE anti-CA titers were significantly suppressed, although their total IgE levels were not significantly different compared to controls. In a second series of experiments, mice which received increased quantities (3 X more) of anti-epsilon had no detectable serum IgE (within 30 days post anti-epsilon treatment), significantly decreased titers of IgE antibody, and reduced numbers of IgE bearing spleen and mesenteric lymph node cells. These studies indicate that anti-epsilon injections in adult mice can significantly alter total and specific IgE levels.     

IgE levels in sera of cancer patients.

Immunoglobulin E (IgE) was measured in the sera of 18 healthy adult volunteer donors, 67 adults with various types of solid neoplasms, and 17 adults with clinical allergy by means of a double-antibody radioimmunoassay. There was no siginificant difference in the geometric mean serum IgE level between all cancer subjects and the healthy control subjects except that cancer and noncancer patients who had definite clinical allergies showed an increased mean IgE level. Similarly, there was no significant difference in the mean IgE level of any of the six cancer subgroups studied when compared to the control mean. Thus, there was no evidence reflected in serum levels that IgE plays a role in the immunopathology of the cancer population tested.     

Ossification in nude mice. 1. Macroscopical study

Ossification was studied in cleared fetuses, newborns, 1- and 6-week-old nu/nu and nu/+ mice of the B 10 LP background. The same ossification pattern was observed in nu/nu and nu/+ in the embryonal period as well as in newborn animals and mice aged 1 or 6 weeks. On the other hand, 6-week-old nu/nu mice exhibited a lower X-ray density of the skeleton and a lower thickness of the proximal tibial growth plate than 6-week-old nu/+ litter mates. The results indicate the influence of postnatal factors on the skeletal development of nu/nu mice.     

Serum levels of IgE in malignant lymphogranulomatosis.

Serum levels of IgE in malignant lymphogranulomatosis (Hodgkin's disease) were lowered in patients who had been intensively treated, without eosinophilic granulocytes, and in less advanced forms of the disease. High levels were observed in untreated patients with eosinophilic granulocytes in their peripheral blood, and in clinically advanced cases.     

Biodistribution of filamentous phage-Fab in nude mice.

In vivo panning of peptide libraries in mice has allowed the isolation of peptides which target the vasculature of specific organs. The application of this approach to phage displaying Fab fragments (phage-Fab) could lead to the isolation of antibodies which recognize novel tumor antigens. In this study, we have evaluated the biodistribution of phage-Fab in nude mice. Balb/c nude mice were injected intravenously with 10(9) TU of phage displaying the anti-colon cancer Fab c30.6. Blood samples were collected at nine time points over a period of 72 h and three groups of four mice were sacrificed at 4 min, 24 h and 72 h. Normal tissues (liver, colon, spleen, kidneys, lungs, skeletal muscle) and faeces were collected at these time points and the number of viable phage in each sample was determined. The distribution of phage in tissues was also examined by immunohistochemical analysis of paraffin-embedded tissues. Regression analysis of plasma kinetic data showed that the half-life and the volume of distribution of phage was 3.6 h and 1 ml, respectively. Phage uptake occurred predominantly in lungs, kidneys, spleen and liver. Relatively few phage were distributed to colon and muscle, and phage were eliminated from the circulation by 72 h. Immunohistochemical analysis showed phage to be mainly within the vasculature at 4 min, whereas notable phage extravasation was observed at 24 h and 72 h. In conclusion, this study provides information on the in vivo behavior of phage-Fab which will be useful in the design of in vivo panning strategies. By choosing appropriate time points for tissue collection, it may be possible to isolate novel Fabs against both intra- and extravascular targets.     

Relation between total serum IgE levels and IgE antibody production in rats.

Five different rat strains were immunized with 100 microgram ovalbumin and 1 mg Al (OH)3. A good correlation was found between the total serum IgE level of a rat strain before immunization and the IgE antibody production. Good IgE antibody-producing strains had high total serum IgE levels and vice versa. A discordance between the evolution of the total serum IgE level after immunization and the changes in IgE antibody level was found in all strains.     

Immunoglobulin levels of sera of genetically thymusless (nude) mice

The immunoglobulin levels of the various mouse immunoglobulin classes in sera of genetically thymusless (nu/nu) mice and their littermate controls with thymus (nu/⁺) were determined. The amounts of IgM in nu/nu and control mice were equal, but the amounts of IgA, IgG₁, IgG_2a and IgG_2b in nu/nu mice of 10 weeks were, respectively, 14, 3, 27 and 14 % of those in control mice. Our results indicate that the presence of an intact thymus is not needed for the production of IgM, but seems to play an important part in the production of IgA and IgG.     

Serum IgE levels in amoebiasis

Elevated levels of serum immunoglobulin E (IgE) are found in many parasitic diseases. In order to determine the influence of Entamoeba histolytica on IgE levels of clinically symptomatic patients with intestinal amoebiasis, a controlled study was performed. There was no difference between the serum IgE values from Brazilian patients with amoebiasis and those from age-, race- and sex-matched normal Brazilian controls. Based also on our previous similar studies on giardiasis and Chagas’ disease, we conclude that protozoan infections do not elevate serum IgE levels.     

Serum IgE levels in giardiasis

Raised levels of serum immunoglobulin E are found in many parasitic diseases. In order to determine the influence of Giardia lamblia on IgE levels of clinically symptomatic patients, a controlled study was performed. There was no difference between the serum IgE values from Brazilian patients with giardiasis and those from normal Brazilian controls, although in both groups there were many individuals with values higher than the normal range reported from the northern hemisphere.