Immunological Functions In Mice Research Articles

Study on immunoregulation function of peony seed proteolysis product in mice.

To explore the immunoregulatory function of peony seed proteolysis product in mice, the protein from peony seed meal was extracted and hydrolyzed with bromelain. The peony seed proteolysis product was fed to mice at three different doses of 0.25, 0.5, and 1.0g/kg for 21days. The immunoregulation abilities of peony seed proteolysis product after each of these doses were evaluated in mice. Our results showed that all immune indices were higher in mice that had received a lavage with peony seed proteolysis product than in control mice. The immune indices of immune organs, delayed-type hypersensitivity reaction (DTH), phagocytosis of peritoneal macrophages, serum hemolysin levels, lymphocyte proliferation (SI value), and levels of IFN-γ and IL-4 in the middle dose and high dose groups were significantly higher (p<.05) or extremely significant(p<.01) in comparison with the control group. These results indicate that the peony seed proteolysis product enhances immunological functions in mice. PRACTICAL APPLICATIONS: Peony seed is rich in proteins and can be extracted and hydrolyzed using bromelain. The peony seed proteolysis product can enhance the nonspecific, humoral, and cellular immune responses. Thus, peony seed could be of potential value to obtain peony seed protein, which can be further developed and utilized in the manufacture of functional health products.

Abstract POSTER-BIOL-1337: Omentum promotes suppression against peritoneal tumors

Abstract Purpose: The metastasis of ovarian cancer to the omentum is associated with poor clinical outcomes. Although the omentum has immune function due to the activities of milky spots, the role of the omentum in anti-tumor immunity has not been rigorously addressed. We hypothesize that the omentum directly modulates anti-tumor immunity to metastasized tumor cells. Experimental procedure: We examined metastases and immunological function in mice that expresses SV40 T antigen oncogene under the Mullerian Inhibitory Substance type II Receptor promoter (MISIIR-Tag). In separate experiments we also implanted 3 x 106 EG7.1.15 cells (murine thymoma that express chicken ovalbumin (OVA)) intraperitoneally (i.p.) to induce peritoneal tumors. We used flow cytometry to analyze cells from the omentum and peritoneal exudate from mice with or without tumors. Results: Omental tumor growth induced by EG7.1.15 cells is associated with an increase in CD4+CD25+FoxP3+ T regulatory cells (Tregs) and CD103+ DCs, while tumor-specific CD8+ T cells are reduced. Although tumor-specific CD8+ T cells generated in the periphery prior to tumor onset prevent omental and peritoneal tumor growth, tumor-specific CD8+ T cells generated after tumors are established in the omentum are unable to mediate tumor clearance. The induction of tolerance requires the omentum, is dependent on FoxP3+ Tregs, is tumor antigen-specific and takes place in as few as 6 days. The metastasis of ovarian tumor cells into the omentum also correlates with an increase in Tregs. Deleting Tregs in both models reduces tumor burden. Conclusions: Metastasis of tumor cells to the omentum leads to immunological tolerance rather than immunity – even when tumor cells express foreign antigens. Thus, the omentum has an immunological activity that prevents, rather than promotes, immunity to peritoneal tumors. Citation Format: Selene Meza-Perez, Maria de la Luz Garcia-Hernandez, Aaron Silva-Sanchez, Javier Rangel-Moreno, Uma Mudunuru, Edith M Lord PhD, Troy D. Randall. Omentum promotes suppression against peritoneal tumors [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1337.

Basic fibroblast growth factor improves cellular immunological functions in mice

Basic fibroblast growth factor (bFGF, FGF-2) is a multifunctional growth factor that has been proved to have important roles in various tissues. Background researches revealed that biological functions of B and T lymphocytes producing bFGF and its receptors were regulated by the cytokine, which implied that bFGF may participate in immune defense. In order to investigate the effects of bFGF on immune functions, the present paper employed mice administrated with bFGF to detect phagocytosis of macrophages, activity of natural killer cell and number of antibody-producing cells in vivo as well as proliferation of spleen cells in vitro. Results showed that the four detected parameters were all significantly upregulated in bFGFtreated mice, which suggested an active role of bFGF occurring in cellular immunity of mice. Moreover, the increment of plaques formed by antibody-producing cells implied that bFGF also has a positive effect upon humoral immunity.

Regulatory effects of Tenebrio molitor Linnaeus on immunological function in mice

This paper describes the results of experiments to test the effect of the larvae of Tenebrio molitor Linnaeus on the immune systems of mice. Mice were given a decoction of T. molitor in water at doses of 1.87, 3.75 and 7.50 g/kg/d for four weeks, after which their immune function was studied. The results indicate that T. molitor observably enhanced the carbon expurgatory index and phagocytic index. The half of hemolysis values in serum of treated mice increased compared to the control group. Furthermore, serum nitric oxide (NO) content in all treatment groups was higher than that of the control group whereas acid phosphatase and alkaline phosphatase activity was only significantly higher in the high dose group relative to the control group. We conclude that T. molitor can enhance the immune function of mice and therefore, this insect has the potential of a health food supplement. Keywords: Tenebrio molitor Linnaeus, mice, immunoregulation, immunological function

Immunomodulatory Activity of the Methanol Extract of &lt;i&gt;Amorphophallus campanulatus&lt;/i&gt; (Araceae) Tuber

Purpose: Traditionally, Amorphophallus campanulatus tuber is used for the treatment of enlarged spleen, rheumatism and tumour. Therefore, this study was designed to evaluate the immunomodulatory activity of the plant material. Method: The effect of the methanol extract (ME) of Amorphophallus campanulatus tuber on immunological function in mice was studied using charcoal clearance, spleen index and delayed-type hypersensitivity (DTH) response models. The extract was administered orally at doses of 250 and 500 mg/kg. Results: The extract exhibited immunomodulatory activity by causing a significant decrease in charcoal clearance, spleen index and delayed-type hypersensitivity (DTH) response. Conclusion: Amorphophallus campanulatus caused decreases in the charcoal clearance rate and cellular immunity by facilitating the footpad thickness response to sheep red blood cell (RBC) in sensitized mice.Keywords: Amorphophallus campanulatus; immunomodulatory activity, Charcoal clearance, Spleen index, Delayed-type hypersensitivity response.

Enhancement of Natural Killer Cell Activity in Healthy Subjects by Immulina®, aSpirulinaExtract Enriched for Braun-Type Lipoproteins

Immulina®, a commercial extract of Arthrospira (Spirulina) platensis is a potent activator of THP-1 monocytes and CD4+ T cells IN VITRO and enhances several immunological functions in mice. We further characterized Immulina® by determining that Braun-type lipoproteins are responsible for a major portion of the IN VITRO monocyte activation exhibited by this material. In order to understand the effect of Immulina® on NK cell activity, a pilot study was conducted on ten healthy North American individuals who supplemented their diet with Immulina® (400 mg/day) for seven days. We observed a 40% average increase in the killing of K562 tumor cells by NK cells (p < 0.01) after Immulina® supplementation. In a separate placebo-controlled, crossover study involving 11 healthy Danish subjects, we observed increased mRNA expression of the NK cell marker NKG2D by 37% (p = 0.02) and by 55% (p = 0.0003) after administration of Immulina® (200 mg and 400 mg per day, respectively) for seven days. The mRNA expression of the NK- and T-cell marker perforin increased by 75% (p = 0.008) after administration of 400 mg Immulina® per day. Both markers displayed significant dose-dependent effects (p = 0.0003 and p = 0.02, respectively). The ratio between CD56 (bright) and CD56 (dim) NK cells was not affected by Immulina® administration. In summary, two independent studies showed enhancement of NK cell activity following administration of Immulina® for seven days.

Immunomodulatory effect of a Sophora subprosrate polysaccharide in mice

The aims of the present study were to investigate the immunomodulatory effect of a Sophora subprosrate polysaccharide (SSP1) on splenic lymphocyte proliferation, production of cytokines and antioxidant capacities in dexamethasone-induced immunosuppressed mice. The results showed that SSP1 stimulated proliferation and IFN-γ secretion of murine splenic lymphocytes at concentrations of 50, 100, 200 or 400 mg/L in vitro. SSP1 increased the levels of interleukin-6 and tumor necrosis factor-α in immunosuppressed mice induced by subcutaneous injection of dexamethasone at 1.25 mg/kg. Administration of SSP1 by intraperitoneal injection significantly raised spleen index, glutathione level, glutathione peroxidase activity and lysozyme activity in the immunosuppressed mice. This suggests that SSP1 may play an important role in regulating immunological functions in mice.

Effect of a seashell protein Haishengsu on the immunological function of mice with Ehrlich ascites tumor

This study was designed to investigate the effect of a seashell protein Haishengsu (HSS) on the immuno logical function in mice with Ehrlich ascites tumor. Ehrlich ascites tumor-bearing mice were divided into three HSS groups (25, 50 and 100 mg/kg, i.v., respectively), cyclophosphamide (10 mg i.p.) and control group. The immunological function was assessed by measuring the phagocytizing capacity of the peritoneal macrophages and neutrophils, as well as the number of spleen hemolytic plaque-forming cells. The percentage of blood T-lymphocytes was also evaluated. The number and the percentage of phagocytizing macrophages and neutrophils in the 50 and 100 mg/kg HSS groups were higher than in the control and the cyclophosphamide groups (P < 0.01). The hemolytic plaque-forming cells in the three HSS groups (10.8 ± 1.2, 16.9 ± 3.9 and 25.3 ± 2.9, respectively), was greater than in the control (7.3 ± 1.4), or the cyclophosphamide group (0.33 ± 0.4) (all P < 0.01). In all HSS groups, the percentage of blood T3, T4 and T8 was higher than in the cyclophosphamide and the control group (all P < 0.01). We conclude that HSS has significant immune-modulating effect in mice with Ehrlich ascites tumor.

Enhancement of Natural Killer Cell Activity and Phagocytosis in Healthy Subjects by Immulina, a Spirulina Extract Enriched for Braun Type Lipoproteins

Immulina is a commercial extract of Spirulina (Arthrospira) platensis that is standardized by biological activity. We previously reported that this extract is a potent activator of THP-1 monocytes in vitro and that oral consumption enhanced several immunological functions in mice [1]. In this study we further characterized Immulina by determining that Braun type lipoproteins are responsible for a major portion of the in vitro monocyte activation exhibited by this material. In order to understand the effect of Immulina on the human immune system, a pilot study was conducted on ten healthy individuals who supplemented their diet with Immulina (400 mg/day) for seven days. Blood was drawn from the participating individuals at two time points: before and after seven days of Immulina supplementation. Changes in mononuclear and polymorphonuclear phagocytosis were determined in heparinized whole blood as well as the cytotoxicity exhibited by natural killer (NK) and lymphokine activated killer cells. We observed statistically significant increases both in tumor cell killing by NK cells (p = 0.0019) and in phagocytosis by blood mononuclear cells (p = 0.0124) after Immulina supplementation. Acknowledgements: This research was partly funded by a USDA, Agricultural Research Service Specific Cooperative Agreement No. 58-6408-012. Immulina capsules were supplied by Scandinavian Clinical Nutrition Denmark A/S, Greve, Denmark.

Immune responses in mice to arecoline mediated by lymphocyte muscarinic acetylcholine receptor

There is evidence that lymphocytes possess all the components of the cholinergic system independent of neuronal innervations. Thus, potential therapeutic applications of drugs targeting the neuronal cholinergic system might have side effects on the immune system. This study investigated whether arecoline could affect immunological functions in mice and explored the mechanism of the effect of arecoline on the immune system. To investigate this, arecoline at the dose of 2mg/kg was administered subcutaneously in BALB/c mice for 4 weeks to evaluate changes in immunological function both in vivo and in vitro. Several indices were used to assess immunological activation, including the spleen index, serum hemolysin levels, interleukin (IL)-2 and splenocyte proliferation. Our results showed a significant reduction in treated animals with respect to the control group in the following tests: the spleen index (86%), hemolysin against sheep red blood cells (68%), IL-2 production (73%), and splenocyte proliferation induced by concanavalin A or lipopolysaccharide (76% and 74%, respectively). The muscarinic receptor antagonist atropine (1mg/kg) reversed the inhibition of the four immune-related parameters mentioned above. Chronic atropine alone did not significantly affect the immune response. To our knowledge, this is the first study to demonstrate that arecoline interferes with the immune system by targeting the muscarinic acetylcholine receptors of the non-neuronal cholinergic system.

Immunological function in mice lacking the Rac-related GTPase RhoG.

RhoG is a low-molecular-weight GTPase highly expressed in lymphocytes that activates gene transcription and promotes cytoskeletal reorganization in vitro. To study the in vivo function of RhoG, we generated mice homozygous for a targeted disruption of the RhoG gene. Despite the absence of RhoG, the development of B and T lymphocytes was unaffected. However, there was an increase in the level of serum immunoglobulin G1 (IgG1) and IgG2b as well as a mild increase of the humoral immune response to thymus-dependent antigens. In addition, B- and T-cell proliferation in response to antigen receptor cross-linking was slightly increased. Although RhoG deficiency produces a mild phenotype, our experiments suggest that RhoG may contribute to the negative regulation of immune responses. The lack of a strong phenotype could indicate a functional redundancy of RhoG with other Rac proteins in lymphocytes.

Immunological function in mice exposed to JP-8 jet fuel in utero.

Immunological parameters, host resistance, and thyroid hormones were evaluated in F1 mice exposed in utero to jet propulsion fuel-8 (JP-8). C57BL/6 pregnant dams (mated with C3H/HeJ males) were gavaged daily on gestation days 6-15 with JP-8 in a vehicle of olive oil at 0, 1000, or 2000 mg/kg. At weaning (3 weeks of age), no significant differences were observed in body, liver, spleen, or thymus weight, splenic and thymic cellularity, splenic CD4/CD8 lymphocyte subpopulations, or T-cell proliferation. Yet, lymphocytic proliferative responses to B-cell mitogens were suppressed in the 2000 mg/kg treatment group. In addition, thymic CD4-/CD8+ cells were significantly increased. By adulthood (8 weeks of age), lymphocyte proliferative responses and the alteration in thymic CD4-/CD8+ cells had returned to normal. However, splenic weight and thymic cellularity were altered, and the IgM plaque forming cell response was suppressed by 46% and 81% in the 1000 and 2000 mg/kg treatment groups, respectively. Furthermore, a 38% decrease was detected in the total T4 serum hormone level at 2000 mg/kg. In F1 adults, no significant alterations were observed in natural killer cell activity, T-cell lymphocyte proliferation, bone marrow cellularity and proliferative responses, complete blood counts, peritoneal and splenic cellularity, liver, kidney, or thymus weight, macrophage phagocytosis or nitric oxide production, splenic CD4/CD8 lymphocyte subpopulations, or total T3 serum hormone levels. Host resistance models in treated F1 adults demonstrated that immunological responses were normal after challenge with Listeria monocytogenes, but heightened susceptibility to B16F10 tumor challenge was seen at both treatment levels. This study demonstrates that prenatal exposure to JP-8 can target the developing murine fetus and result in impaired immune function and altered T4 levels in adulthood.

The inhibitory effect of Sinomenine on immunological function in mice

AbstractSinomenine, an alkaloid isolated from the stem of Sinomenium acutum (Thunb.) Rehd. et Wils., is reported to have clinically good curative effects on arthritis and rheumatoid arthritis. Our investigation has shown that sinomenine inhibits both the humoral and cellular immunity of mice. The weights of spleen and thymus of mice treated with sinomenine (50–150 mg/kg/d, i.p.) were drastically reduced. The antisheep red blood cell antibody production and delayed‐type hypersensitivity reaction induced by sheep red blood cells were inhibited by sinomenine at doses of 50, 100 and 150 mg/kg/d; and the survival time of split‐heart transplants was also prolonged. In vitro, sinomenine suppressed the proliferation of splenic cells stimulated with LPS and ConA. These immunosuppressive actions of sinomenine afford a reasonable explanation for its clinical effects in the treatment of arthritis and rheumatoid arthritis.

Effect of soft x-ray irradiation on immunological functions in mice.

Effect of soft x-ray irradiation on immunological functions in mice was investigated. Soft x-ray irradiation with 100R or more induced a significant reduction in the number of plaque-forming cells (PFC). The reduction in the number of PFC depended on the irradiation doses. Irradiation with 600R or more showed a significant reduction in the delayed reaction of footpad swelling. However, soft x-ray irradiation with doses ranging from 100R to 1000R did not exert significant influence on the K values of carbon clearance test. Irradiation with 100R or more of soft x-ray showed a remarkable reduction of response to concanavalinA (ConA) or lipopolysaccharide (LPS) in spleen cells, and the response to ConA was lower than that to LPS. These results suggest that in the soft x-ray-irradiated mice, antibody-producing ability, delayed type hypersensitivity reaction and mitogenic activity are sensitive to soft x-ray irradiation and furthermore, T cell is more sensitive than B cell, but phagocytic activity of reticulo-endothelial system (RES) is resistant to soft x-ray irradiation.

Heart and liver lipid fatty acid and behavior changes in mice after a diet change

270-Day old, male Ham/ICR mice were subjected to a diet change from high protein and carbohydrate and low fat to a diet higher in fat and lower in carbohydrate and protein. Age matched mice were maintained on laboratory rodent chow as controls. The diet change was not defined so the observed differences could not necessarily be ascribed to altered protein, carbohydrate, or fat intake. Comparison of the controls with the experimental mice revealed the “junk food” mice differed in lipid fatty acid profiles of the heart and liver and in percentage of lipid palmitic and oleic acids in these organs and also in plasma. Appearance was altered in the experimental mice which had dull, greasy coats. In addition, the experimental animals were less active, slept singly, and were slower in negotiating a three-choice maze than their comparably housed counterparts, indicating altered activity/curiosity behavior. It has been clearly demonstrated that dietary manipulation affects many aspects of body function in animals and humans. For example, nutrition and/or caloric intake affects kidney disease (1), myocardial fibrosis (2), the prevalence of neoplasms (3), learning behavior in rats (4,5), immunological function in mice (6), liver metabolism as exemplified by diet regulated lipogenic activity in rat liver (7–10), morphological effects on the central nervous system (11), and hepatic enzyme activity (12). An intriguing effect of diet is it possible role in aging. Increased longevity in rodents is clearly correlated with certain early diet deprivations (13,2). Rapid growth rate appears to have an adverse effect on longevity, and some typical biochemical changes associated with aging are delayed by a restricted diet. There may also be mesureable biochemical links between diet and quality of life in terms of function. Harmon (14) fed rats from 2 months to senescence (up to 35 months) diets varied in saturated fats. There was no effect on longevity, but the higher the unsaturated fat content in the diet, the worse the performance of the animal in a closed field maze. It was speculated that increased unsaturation in lipid membranes increased suseptibility to free radical damage which affected CNS function. It is not clear why the presumed stimulation of lipid peroxidation by the presence of unsaturated fats did not have an effect on longevity, as one might reasonably assume that the adverse effects on membranes caused by lipid ixidation would promote neoplasms, organs dysfunction, and disease. Body lipids appear to play a role in quality of life and, possibly, aging, particularly in their important role in membrane function. Therefore, it seemed useful to document the response of heart, liver, and plasma lipids to a sudden diet change in a fully mature animal where maturation processes were not a factor. In addition, a “supermarket” diet (15) was used with the idea it would parallel the eating habits of some middle age Americans. The unexpected results of this preliminary study were a marked change in curiosity/activity behavior and a dramatic change in appearance of the mice on the junk food diet. Also found were highly significant increases in specific lipids in the heart and liver as well as in the percent of oleic and palmitic acids in plasma and in some classes of heart and liver lipids.

Immunological function in mice chronically exposed to nitrogen oxides (NO x)

BALB c mice were exposed to 10 ppm NO or NO 2 for 2 hr daily on weekdays, for varying periods up to 30 weeks. At intervals of approximately 7 weeks, groups of animals were subjected to a variety of pathological and immunological examinations: serum antibody responses to both T-dependent and T-independent antigens, spleen cell PHA and graft-versus-host responses, capacity to reject a transplanted tumor, routine hematology, and lung pathology. Tests of immune function indicated suppression resulting from chronic exposure to these gases, and in most cases data indicated enhancement of immunological reactivity by shorter exposures. NO 2 appeared somewhat more potent than NO in this regard, but the differences observed were not great. Chronic NO exposure produced a more severe lung pathology, with clear evidence of paraseptal emphysema.