Activity Of Peritoneal Exudate Cells Research Articles

Effects of Social Hierarchy Establishment on Stress Response and Cell Phagocytosis in Gilt-Head Sea Bream (Sparus aurata)

Social stress can affect the ability of fish to respond to various stressors, such as pathogens or environmental variations. In this paper, the effects of social stress on gilt-head bream (Sparus aurata) were investigated. To study the effects of physiological stress, we evaluated biochemical and cellular parameters, such as cortisol, glucose, lactate, osmolarity, and phagocytosis, 24 h after the establishment of social hierarchy in a group of three fish. Social hierarchy was determined and characterized by behavioral observation (aggressive acts and feeding order) of the specimens (dominant: “α”; subordinate: “β” and “γ”). After the establishment of social hierarchy, we observed that, overall, levels of plasma cortisol and other biochemical plasmatic stress markers (glucose and lactate) were higher in subordinate individuals than in dominant individuals. In addition, the modulation of phagocytic activity of the peritoneal exudate cells (PECs) demonstrated that social stress appeared to affect immune response. Finally, principal component analysis clearly separated the subordinate fish groups from the dominant groups, based on stress markers and the phagocytic activity of peritoneal exudate cells. This study contributes to current knowledge on gilt-head sea bream, helping to understand the link between social stress, behavior, and physiology of this species, relevant in the aquaculture sector, where fish are subjected to several kinds of stress.

Formation of Neutrophil Extracellular Traps when Modeling Plague Infection in Mice Immunized with Yersinia pestis EV NIIEG

The purpose of the study was to determine the effect of Yersinia pestis EV NIIEG on the process of neutrophil extracellular traps formation in vivo when modeling plague infection and assess their contribution to antiplague protection.Materials and methods. BALB/c mice, which were immunized subcutaneously with the Y. pestis EV NIIEG vaccine strain, were used in the study. Animals were infected with a virulent strain Y. pestis 231 at a dose of 20 LD50 (103 CFU). To evaluate the contribution of neutrophil extracellular traps (NETs) to antibacterial protection, an experimental model was used based on fermenting NETs in the abdominal cavity of mice with nuclease. To calculate the number of NETs in peritoneal exudate (PE) fluorescent microscopy was applied. Phagocytic activity of PE cells was determined by flow cytometry. Bactericidal effect of NETs was recorded using bacteriological method.Results and discussion. In pre-immunized mice, the process of NETs formation in response to the reintroduction of plague microbe living cells was 5 times more intense than in intact animals and was accompanied by a significant increase in the killing of Y. pestis cells in PE. The use of micrococcus nuclease in the experiment for fermentation of the NETs, produced in the body of immunized animals, provided evidence of NET participation in conferring anti-infective protection against plague infection. Thus, the established fact of the NET formation in case of Y. pestis infection of mice immunized with Y. pestis EV NIIEG vaccine strain and the influence of this process on the effectiveness of protection against plague is the basis for further clarifying the immunopathogenetic role of neutrophil granulocytes in plague.

The Metabolic Activity of Innate Immunity Cells in Experimental Infection Caused by Various Plasmid Types of Yersinia Pseudotuberculosis

In a comparative aspect, the functional state of inflammation effector cells in animals infected with various plasmid types of Yersinia pseudotuberculosis was studied. The metabolic activity of peritoneal exudate cells has been investigated in an experimental infection caused by four plasmid types of Y. pseudotuberculosis: type 82⁺: 48⁺, containing two plasmids pVM 82 and pYV; type 82⁺: 48- containing single pVM 82 plasmid; type 48⁺: 82^- containing single pYV plasmid; plasmid-free type 48^-: 82^-. The parameters of enzyme activity (ATP-ase, 5'-nucleotidase, lactate dehydrogenase, myeloperoxidase) and the level of nitric oxide metabolites were determined. The variability of the metabolic activity of the cells in the inflammatory focus (peritoneal exudate containing neutrophils and macrophages) in infected animals has been established. In response to infection with Y. pseudotuberculosis strain containing two plasmids pYV and pVM82, the production of the nitric oxide metabolites, rather than the active forms of oxygen, had the primary importance in providing the bactericidal potential of phagocytes, compared to animals infected with a strain containing a single pVM82 plasmid. It was concluded that a special biological effect associated with the pVM 82 plasmid available in the Far Eastern strains of the causative agent of epidemic pseudotuberculosis (Far Eastern scarlet-like fever) was involved in the provision of predominantly nitroxide-dependent bactericidal mechanisms of innate immunity cells in this infection.

Studying the spectrum of immunotropic action of Pletnev drops No 60 (Phospholiten)

The purpose of the present work was studying of immunomodulating activity of Pletnev drops No 60. On the basis of the received results it is established that Pletnev drops No 60 possess immunomodulatory properties, stimulates humoral and cellular immunity, the bactericidal activity of peritoneal exudate cells of mice, bactericidal activity of phagocytes of peripheral blood, promote production of TNF-α by mononuclear cells, the number of peripheral blood leukocytes of mice. Pletnev drops No 60 increase the survival of animals. Pletnev drops No 60 possess antioxidant properties and, under his influence, the observed suppression of spontaneous and simhasan-induced of chemiluminescence of peripheral blood leukocytes of mice and suppression of luminol-dependent and lucigenin-dependent spontaneous and simhasan-induced of chemiluminescence of leukocytes of man.

Immune Response Against Sporothrix schenckii in TLR-4-Deficient Mice

For many fungal diseases, macrophages are the major cell population implicated in host protection, primarily by their ability to eliminate the invading fungal pathogen through phagocytosis. In sporotrichosis, this remains true, because of macrophages’ ability to recognize Sporothrix schenckii through specific receptors for some of the fungus’ cellular surface constituents. Further confirmation for macrophages’ pivotal role in fungal diseases came with the identification of toll-like receptors, and the subsequent numerous associations found between TLR-4 deficiency and host susceptibility to diverse fungal pathogens. Involvement of TLR-4 in immune response against sporotrichosis has been conducted to investigate how TLR-4 signaling could affect inflammatory response development through evaluation of H2O2 production and IL-1β, IL-6 and TGF-β release during the course of S. schenckii infection on TLR-4-deficient mice. The results showed that macrophages are largely dependent on TLR-4 for inflammatory activation and that in the absence of TLR-4 signaling, increased TGF-β release may be one of the contributing factors for the abrogated inflammatory activation of peritoneal exudate cells during mice sporotrichosis.

Tumoricidal Effects of β-Glucans: Mechanisms Include Both Antioxidant Activity Plus Enhanced Systemic and Topical Immunity

A study to evaluate the mechanisms of tumoricidal activity resulting from orally administered extract of Agaricus blazei Murill (A. blazei) was performed in mice bearing syngeneic and xenogeneic tumors. Tumor regression was comparably seen in both syngeneic and xenogeneic tumor-bearing mice when administered oral extract preparations. In addition, in a murine syngeneic tumor model, oral administration of water-soluble extracts of A. blazei resulted in significant production of cytokines such as IFN-γ, and TNF-α in peritoneal exudate cells, in parallel with the marked regression of tumor development. The water-soluble extracts also induced pronounced antioxidant activity in in vitro and in vivo assays using two different methods. These results indicate the A. blazei extract may enhance not only the immnunomodulatory effects that promote activity of peritoneal exudate cells for tumor regression but also potentially result in the direct destruction of tumor cells through its antioxidant activity.

Modulatory Effect of Killed Propionibacterium acnes and Its Purified Soluble Polysaccharide on Peritoneal Exudate Cells from C57Bl/6 Mice: Major NKT Cell Recruitment and Increased Cytotoxicity

Propionibacterium acnes has been described as a potent adjuvant to immune responses in vitro and in vivo. Presently, we analysed the modulation of peritoneal exudate cells (PEC) by heat-killed P. acnes or its purified soluble polysaccharide (PS), both injected intraperitoneally in C57Bl/6 mice, aiming at their recruitment and cytotoxicity. Both treatments induced an increase in macrophages, immature dendritic cells, B1a lymphocytes and NK1.1(+) CD3(+) cells. The bacterium caused a remarkable increase in a NK1.1(+) CD3(+) CD4(-) CD8(-) cells subpopulation, whereas the PS component seemed responsible for the recruitment of mainly macrophage cells. To assess P. acnes and PS adjuvant effect on PEC cytotoxicity we evaluated their in vitro effect on murine B16F10 melanoma cells. The effector cells from the heat-killed bacteria and PS-treated groups lysed melanoma cells in co-cultures with PEC. Mice genetically deficient in IFN-gamma, when stimulated with P. acnes or PS, had reduced PEC cytotoxicity, and the cytotoxic effect was completely abrogated in PEC from iNOS(-/-) mice. The tumoricidal activity of PEC from P. acnes-treated mice was mediated by macrophages and NKT cells stimulated with IL-12. In PS-treated mice the cytotoxicity was mediated mainly by macrophages. Moreover, both treatments increased IL-4 and IFN-gamma production by NKT cells. In conclusion, we show that P. acnes act mainly by recruiting and activating NKT double-negative cells in PEC, which were shown to be tumoricidal in vitro when induced by IL-12. Macrophages induced by both P. acnes and PS have their antitumour effect dependent on NO production.

Effect of farmorubicin both free and associated with poly(butylcyanoacrylate) nanoparticles on phagocytic and NK activity of peritoneal exudate cells from tumor-bearing mice

The effect of Epirubicin (farmorubicin, FR), either free or associated with poly(butylcyanoacrylate) nanoparticles (PBCN) upon the phagocytic and natural killer (NK) activity of peritoneal exudate cells (PECs) harvested from Lewis lung carcinoma (LLC)-bearing-mice was investigated. Phagocytic and NK activity were tested 72 and 96 h, respectively after the last four intraperitoneal (i.p.) injections of the tested compounds have been administered to the mice. Phagocytic activity was evaluated in vitro by phagocytic index and ingestion capacity using a phagocytic assay. NK activity was evaluated in a direct cytotoxic test, in which PECs were used as effector cells while human erythroleukemic K-562 cells were used as target cells. The phagocytic activity of PECs, harvested from tumor-bearing mice, was stimulated after treatment with FR free, FR associated with polymer nanoparticles and with unloaded PBCN. The NK activity of PECs was strongly stimulated by unloaded PBCN. FR both free and encapsulated into the polymer matrix during the polymerization of n-butylcyanoacrylate (n-BCA) stimulated the NK activity of PECs, while FR adsorbed onto nanoparticles restrained it. These results suggest that the association of FR with nanoparticles modifies selectively its immunomodulating ability without producing any significant immunological disturbances. The toxicity of some of FR polymer forms towards PECs, displaying NK activity, probably comes from the enhanced local drug concentration on the membrane surface of the immune cells. However, it is insufficient to preclude the use of nanoparticles as drug delivery system.

Recovery of age‐dependent immunological deterioration in old mice by thyroxine treatment

On the basis that multiple interactions exist between thyroid hormones and immune system, and ageing is accompanied by changes in thyroid hormone secretion, it seems possible that thyroid hormones may be involved in the age-related immune dysfunction. The present study was conducted to evaluate in vivo and in vitro effects of thyroxine (T(4)) treatment on both cell-mediated and humoral immune responses of aged mice. In a trial to improve age-associated immune dysfunction, T(4) (0.2, 1.0 and 5.0 microg) was subcutaneously supplemented to BALB/c mice (over 18 months old) for 30 consecutive days. The present results showed that exogenous treatment of aged mice with T(4) was associated with a marked increase in serum T(4) level, and the total number of peripheral blood leukocytes as well as the total cellularity of thymus, spleen, peripheral lymph nodes (PLNs), mesenteric lymph nodes (MLNs) and bone marrow (BM). T(4) treatment also caused a significant increase in the total and differential numbers of peritoneal exudate cells (PECs), while it caused a slight increase in macrophages' phagocytic activity of PEC. Moreover, T(4) treatment elicited a statistically significant increase in both plaque-forming cell and rosette-forming cell responses. In vitro results showed that the addition of T(4) at concentrations of 0.001, 0.005 and 0.025 microg/well substantially potentiated the ability of splenocytes from aged mice to proliferate in the presence of concanavalin-A mitogen. Histological examination of thymuses from T(4)-treated aged mice revealed that the cortex was preferentially enlarged and repopulated with immature thymocytes. The present study postulates that thyroid hormones may be involved in the observed decrease in the immune responsiveness during ageing, and that T(4) treatment to aged mice is able to restore the age-related decline of the immune efficiency.

Immunogenicity and anti- Burkholderia pseudomallei activity in Balb/c mice immunized with plasmid DNA encoding flagellin

Plasmid DNA encoding the flagella protein (flagellin) was used as a vaccination candidate for the evaluation of its immunogenicity and for protection against infection with Burkholderia pseudomallei. Firstly, flagellin encoding plasmid DNA was injected into Balb/c mice intramuscularly and this elicited both a humoral and a cellular immune response. Total IgG production and the clonal expansion of the spleen cells increased in response to flagellin. The IgG subclass response exhibited a dominance of IgG2a over IgG1 in the sera. In addition, IFN-γ-secreting cells in the spleen were substantially increased. Furthermore, the anti- B. pseudomallei activity of the peritoneal exudate cells was evaluated by a Transwell tissue-culture plate system where the macrophage-activating related cytokines in upper chamber were allowed to cross the plate's membrane and stimulate the activation of peritoneal exudate cells in lower chamber. Our results indicated that the activated peritoneal exudate cells were able to restrict the growth of B. pseudomallei in vitro. Indeed, subsequent intravenous challenge of the vaccinated Balb/c mice with 10 5 CFU of B. pseudomallei resulted in the number of bacterial cells detected in liver and/or spleen being significantly reduced in the flagellin plasmid DNA vaccinated mice. At 7 days subsequent to infection of B. pseudomallei, 5/6 (83%) of flagellin plasmid DNA vaccinated mice had survived. We suggest that plasmid DNA-encoding flagellin might be useful as a potential immunization route for the future development of a vaccine against melioidosis in related animals.

Immunotoxicological effects of piperine in mice

The immunotoxicological effects of piperine were investigated in Swiss male mice, gavaged at a dose of 1.12, 2.25 or 4.5 mg/kg body weight for five consecutive days. All the dose levels had no overt toxic effect and the liver gained weight normally. Treatment at highest dose, however, resulted in significant decrease in the weight of spleen, thymus and mesenteric lymph nodes, but not of peripheral lymph nodes. All the dose levels suppressed the cellular population of lymphoid organs, except for the spleen, where the doses of 1.12 and 2.25 caused an increase. Haematologically, doses of 2.25 and 4.5 mg/kg caused a significant reduction in total leucocyte counts and differential leucocyte counts showed an increase in the percentage of neutrophils. The higher doses of 2.25 and 4.5 mg/kg suppressed the mitogenic response of B-lymphocyte to lipopolysaccharide. The number of primary antibody (IgM) forming cells in the spleen and the level of primary antibody in serum, was decreased. The doses of 1.12 and 2.25 mg/kg suppressed the mitogenic response of T-lymphocytes to phytohaemagglutinin and the nitroblue tetrazolium (NBT) dye reducing activity of peritoneal exudate cells (PECs). Since the lowest dose of 1.12 mg of piperine per kg body weight had no immunotoxic effect, it may be considered as immunologically safe "no observed adverse effect level (NOAEL)" dose.

Doxorubicin induces specific immune functions and cytokine expression in peritoneal cells.

To examine the basis of the immune modulation induced by the anticancer agent doxorubicin (DOX), the immunophenotype, tumoricidal activity, cytokine protein and mRNA expression were determined using peritoneal exudate cells (PEC) from saline-treated (untreated) and DOX-treated mice. A greater percentage of PEC from DOX-treated mice than from untreated mice were adherent to plastic, had characteristics of granulocytes, and were positive for the NK1.1, CD11b/Mac-1, and CD3 markers. DOX decreased the percentage of CD45R/B220+ cells. PEC from DOX-treated mice had greater tumoricidal potential than those from untreated mice since IL2, LPS, or IFNgamma alone increased the cytolytic activity of PEC from DOX-treated mice, whereas PEC from untreated mice required both LPS and IFNgamma to become cytolytic. DOX treatment modulated the expression of specific cytokines. Following stimulation in culture, PEC from DOX-treated mice produced more TNF, IL1, and IFNgamma than PEC from untreated mice. DOX treatment increased the levels of TNF, but not IL1, mRNA and decreased the levels of IL6 mRNA and protein. These data demonstrate that a single DOX injection induces specific effects in PEC and, as a consequence, increases the tumoricidal potential of cells of the macrophage and natural killer types.

Study on the effect of polybutyl-2-cyanoacrylate nanoparticles and their metabolites on the phagocytic activity of peritoneal exudate cells of mice

The phagocytic activity of peritoneal exudate cells (PECs) harvested from peritoneal cavity of mice after a single intraperitoneal (i.p.) treatment with poly(butylcyanoacrylate) nanoparticles (PBCN) and their probable metabolites [poly(cyanoacrylic acid) (PCAA) and n-butanol] was investigated in an in vitro phagocytic assay. Polymer suspension of PBCN was given as a single i.p. injection at doses of 200 and 10 mg kg −1, 3, 18, 72 and 120 h before the performance of the phagocytic assay. PCAA and n-butanol were given at the same manner at doses of 126.8 and 96.8 mg kg −1, respectively (equivalent to a dose of 200 mg kg −1 of intact PBCN after enzyme hydrolysis) 3, 18 and 120 h before the test performance. The phagocytic assay was performed in vitro in tubes with sheep red blood cells (SRBC). Phagocytic index (percentage of PECs ingested more than 3 sheep erythrocytes), phagocytic number, and ingestion capacity (number of erythrocytes ingested per cell) were the parameters used for evaluation of the phagocytic activity. The alterations of phagocytic activity of the PECs observed were strongly time- and dose-dependent. Administration of all tested compounds shortly before the test performance resulted in a considerable decrease in the capability of PECs to ingest SRBC. The alterations of phagocytic activity decreased when the time between the treatment of mice and the phagocytic assay is on the increase. The dose of 200 mg kg −1 of PBCN administered 120 h before the phagocytic assay led to the significant increase of the phagocytic index of PECs. The phagocytic function of assayed PECs was temporary impeded and 5 days were completely enough for their restoration.

Construction and analysis of new vector systems with improved interleukin-18 secretion in a xenogeneic human tumor model.

Interleukin (IL)-18 plays an important role in enhancing cellular immunity against cancer and bacteria. We constructed retroviral and adenoviral vectors that show improved secretion of bioactive murine IL-18 that could further enhance antitumor immunity in a murine model. Secretion of bioactive IL-18 was facilitated by fusing the leader sequences of prepro-parathyroid hormone (PTH) or IL-1 receptor antagonist (IL-1ra) to the 5; end of the mature murine IL-18 cDNA. Transfectants established by the retroviral vector carrying IL-1ra/IL-18 hybrid showed about 100-fold more IL-18 production and interferon (IFN)-gamma induction from splenocytes when compared with those carrying PTH/IL-18 hybrid. Repeated intraperitoneal injection of an adenoviral vector with IL-1ra/IL-18 hybrid ligated to IL-18 (Ad.IL-1ra.IL-18) successfully prevented establishment of human colon cancer cells in the abdominal cavity of mice. Treatment with Ad.IL-1ra.IL-18 was associated with significantly elevated levels of serum IL-18 and IFN- gamma. IL-18 administration also enhanced the cytostatic activity of peritoneal exudate cells against cancer cells. These improved viral vectors, which efficiently produce bioactive IL-18, could be used as a useful tool for cancer gene therapy.

Dietary Effect of .ALPHA.-Tocopherol and Tocotrienols on Lipid Metabolism and Immune Function of Aged Sprague-Dawley Rats.

Eight-month-old male Sprague Dawley rats were fed diets containing α-tocopherol (Toc) or tocotrienol (T3) mixture (composed of 20.5% α-Toc, 21.4% α-T3, 36.5% γ-T3 and other analogs) at the 0.1 or 0.5% level for 3 weeks to examine their dietary effects on lipid metabolism and immune indices. Feeding of α-Toc and T3 significantly de-creased liver phosphatidylcholine peroxide and serum phospholipid levels. In the regulation of immunoglobulin level, significant increase in serum IgA level was observed in the rats fed α-Toc or T3, but the effect on immunoglobulin productivity from spleen and mesenteric lymph node (MLN) was not as marked. Feeding of α-Toc and T3 significantly decreased LTB4-releasing activity of peritoneal exudate cells without decreasing arachidonic acid level. The suppression of LTB4 release was more marked in the rats fed 0.1% α-Toc or T3 than in these fed them at the 0.5% level. When animals were killed after 10 h of fasting, T3 was detected only in MLN and epidydimal adipose tissue. These results suggest that T3 modulates lipid metabolism and immune functions as well as α-Toc, and that MLN and adipose tissue are the main target tissues of T3.

A schistosome-expressed immunomodulatory glycoconjugate expands peritoneal Gr1(+) macrophages that suppress naive CD4(+) T cell proliferation via an IFN-gamma and nitric oxide-dependent mechanism.

Lacto-N-fucopentaose III (LNFPIII) is found in human milk and on the Th2 driving helminth parasite Schistosoma mansoni. This pentasaccharide drives Th2-type responses in vivo and in vitro when conjugated to a carrier. In an attempt to further understand early events in Th1 to Th2 switching, we examined phenotypic and functional changes in peritoneal cell populations in BALB/c and SCID mice following LNFPIII-dextran injection. We found that i.p. injection with LNFPIII-dextran resulted in rapid (<20 h) expansion of the Gr1(+) subpopulation of F4/80(+)/CD11b(+) peritoneal cells, comprising up to 75% of F4/80(+)/CD11b(+) peritoneal cells compared with 18% in uninjected or dextran-injected mice. Functionally, these cells suppressed anti-CD3- and anti-CD28-induced proliferation of naive CD4(+) T cells. LNFPIII-dextran also expanded functional Gr1(+) suppressor macrophages in SCID mice, demonstrating that expansion and function of suppressor cells did not require T cells. Suppression in both BALB/c and SCID mice was NO and IFN-gamma dependent, as addition of inhibitors of inducible NO synthase (N(G)-monomethyl-L-arginine), as well as anti-IFN-gamma Abs, restored the ability of CD4(+) T cells to proliferate in vitro. Depletion of the F4/80(+) subset of Gr1(+) cells eliminated the suppressive activity of peritoneal exudate cells showing that these cells were macrophages. Thus, LNFPIII-dextran rapidly expands the Gr1(+) suppressor macrophage population in the peritoneal cavities of otherwise naive mice. These Gr1(+) cells suppress proliferation of naive CD4(+) T cells in an NO-dependent mechanism, and may play a regulatory role in the switching of Th1- to Th2-type responses.

A Macrophage Protein, Ym1, Transiently Expressed during Inflammation Is a Novel Mammalian Lectin

Oral infections of mice with Trichinella spiralis induce activation of peritoneal exudate cells to transiently express and secrete a crystallizable protein Ym1. Purification of Ym1 to homogeneity was achieved. It is a single chain polypeptide (45 kDa) with a strong tendency to crystallize at its isoelectric point (pI 5.7). Co-expression of Ym1 with Mac-1 and scavenger receptor pinpoints macrophages as its main producer. Protein microsequencing data provide information required for full-length cDNA cloning from libraries constructed from activated peritoneal exudate cells. A single open reading frame of 398 amino acids with a leader peptide (21 residues) typical of secretory protein was deduced and later deposited in GenBank (accession number M94584) in 1992. By means of surface plasmon resonance analyses, Ym1 has been shown to exhibit binding specificity to saccharides with a free amine group, such as GlcN, GalN, or GlcN polymers, but it failed to bind to other saccharides. The interaction is pH-dependent but Ca2+ and Mg2+ ion-independent. The binding avidity of Ym1 to GlcN oligosaccharides was enhanced by more than 1000-fold due to the clustering effect. Specific binding of Ym1 to heparin suggests that heparin/heparan sulfate may be its physiological ligand in vivo during inflammation and/or tissue remodeling. Although it shares approximately 30% homology with microbial chitinases, no chitinase activity was found associated with Ym1. Genomic Southern blot analyses suggest that Ym1 may represent a member of a novel lectin gene family.

Ｓｐｒａｇｕｅ‐Ｄａｗｌｅｙラットの免疫機能に及ぼす玄麦玄米酢摂食の効果

To clarify the immunoregulatory activity of Genbakugenmaisu, a vinegar product produced from brown wheat and rice, LTB4 releasing activity of peritoneal exudate cells isolated from Sprague-Dawley rats was examined in the presence of the vinegar and found that the vinegar suppressed LTB4 release of the cells. Then, Sprague-Dawley rats were allowed free access to the water containing the vinegar at the 0, 0.5, 1.0, or 2.0% level for 3 weeks. Although Genbakugenmaisu intake did not affect to LTB4 productivity of the PEC, it not only elevated serum IgA and IgM levels, but also enhanced IgA, IgG and IgM productivity of mesenteric lymph node lymphocytes of the rats. These results suggest that the vinegar enhance immune function of the rats through activation of immunoglobulin production.

Enhancing effect of an inhibitor of nitric oxide synthesis on bacillus Calmette-Guerin-induced macrophage cytotoxicity against murine bladder cancer cell line MBT-2 in vitro.

We studied the effect of an inhibitor of nitric oxide (NO) synthesis, NG‐monomethyl‐L‐arginine (LNMMA), on the Bacillus Calmette‐Guérin (BCG)‐induced antitumor activity of murine peritoneal exudate cells (PEC) against murine bladder cancer cell line MBT‐2 in vitro. L‐NMMA enhanced BCG‐induced cytotoxic activity of PEC, as well as interferon (IFN)‐γ and tumor necrosis factor (TNF)‐α production. The L‐NMMA‐induced enhancement was due to the prolonged survival of BCG in macrophages, because no enhancement of cytotoxicity was observed and neither IFN‐γ nor TNF‐α production was significantly enhanced by killed BCG. Anti‐TNF‐α antibody (Ab) and anti‐IFN‐γAb reduced the L‐NMMA‐induced enhancement of the cytotoxicity. The depletion of T cells from PEC reduced the production of both IFN‐γ and TNF‐α, as well as the enhancement of cytotoxicity induced by viable BCG plus L‐NMMA. These results suggest that L‐NMMA has an enhancing effect on BCG‐induced macrophage cytotoxicity and the enhancement is partially mediated by T cells and their soluble products. Accordingly, NO inhibitor should be a valuable adjunct to BCG immunotherapy for bladder cancer.

Recent topics in anti‐oxidative factors

Lipids and anti-oxidative factors regulate immune functions such as immunoglobulin production and chemical mediator release. For example, polyunsaturated fatty acids (PUFA) enhance IgE production of isolated rat lymphocytes, but not in the presence of alpha-tocopherol. In addition, anti-oxidative factors such as tea polyphenols and flavonoids exert inhibitory effect on chemical mediator release from rat peritoneal exudate cells (PEC). Some of these immunoregulatory activities of food components could be expressed in vivo. Oral administrations of perilla and fish oils or tea polyphenols led to a significant decrease of LTB4 releasing activity of rat PEC, but IgE production enhancing activity of PUFA was not expressed in vivo. On the other hand, alpha-tocopherol feeding enhanced serum IgA level as well as IgA productivity of mesenteric lymph node lymphocytes. These results suggest that dietary fats and antioxidants are effective for the alleviation of allergic symptom and activation of immune functions.