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3 Nutritional Immunology Laboratory, 4 Comparative Biology Unit, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111; and 5 State Key Laboratory for Infectious Disease Prevention and Control, National Institute of Communicable Disease Control and Prevention, China CDC, 102206 Beijing, China
* To whom correspondence should be addressed. E-mail: dayong.wu{at}tufts.edu.
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ABSTRACT |
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 TOP ABSTRACT IntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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and tumor necrosis factor-
(TNF) production, but only tended to increase IL-2 (P = 0.09) and did not affect IL-10 production by splenocytes. There were significant correlations between NK activity and production of IFN (r = 0.615, P < 0.001) and TNF (r = 0.423, P = 0.032) in splenocytes. Mushroom supplementation did not affect macrophage production of IL-6, TNF, prostaglandin E2, nitric oxide, and H2O2, nor did it alter the percentage of total T cells, helper T cells (CD4+), cytotoxic or suppressive T cells (CD8+), regulatory T cells (CD4+/CD25+), total B cells, macrophages, and NK cells in spleens. These results suggest that increased intake of white button mushrooms may promote innate immunity against tumors and viruses through the enhancement of a key component, NK activity. This effect might be mediated through increased IFN and TNF production.
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Introduction |
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TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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The substances present in mushrooms with immunomodulatory and antitumor activity are mainly polysaccharides (in particular ß-D-glucans), polysaccharopeptides, and polysaccharide proteins (10,12–14). Mushrooms also contain a spectrum of nutrients at varied levels, such as B vitamins, vitamin D, and minerals (potassium, copper, magnesium, selenium, and zinc). In recent years, the consumption of mushrooms, either as whole mushrooms or extracted supplements, has increased. Although historically, mushroom consumption has been associated with the maintenance of health and warding off disease, scientific data supporting their health benefits are limited. Epidemiological data regarding the health benefits of mushroom consumption is essentially nonexistent.
Studies relating the mushroom's medicinal use started 
4 decades ago, and some clinical and experimental studies thus far have suggested that mushrooms and their polysaccharide components inhibit tumor growth. This effect of mushrooms may be due to their ability to modulate immune system function rather than having a direct effect on cancer cells (8,9,11). In the majority of early studies, purified mushroom polysaccharides were administered through a parental route or added to cell cultures. More recent studies, however, reported that oral supplementation with a variety of different mushroom species are effective in modulating certain immune functions (7,9,15,16).
Mushroom products have been evaluated for their pharmaceutical potential, and studies thus far have predominantly focused on tumor-bearing animals or cancer patients. Whether an increase in the dietary consumption of mushrooms or mushroom supplements can also have an impact on healthy animals or subjects has not been established. This is despite the fact that mushrooms and their subcomponents are widely consumed by the general population as part of a normal diet. A majority of studies on mushrooms have been conducted outside of the U.S and almost all have used exotic mushrooms. In contrast, few studies have evaluated the potential health benefits of white button mushrooms (Agaricus bisporus), a strain of mushroom that constitutes 90% of mushrooms consumed in the U.S. Furthermore, little is known about their potential immunological effects. Because the mushrooms of different strains have a varied composition of nutrients and other functional ingredients, the results obtained from studies of these strains might not be applicable to white button mushrooms. Our objective in this study, therefore, was to determine the effect of white button mushrooms on innate and T cell–mediated immune functions.
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Materials and Methods |
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TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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Animals. Male C57BL/6JNIA mice (4 mo of age) were purchased from the National Institute on Aging colonies at Harlan Sprague Dawley. After a 2-wk acclimation period, all mice were weight-matched and placed into 1 of 3 experimental groups. Mice were housed individually and maintained in an environmentally controlled atmosphere (temperature 23°C, relative humidity 45%) with a 12:12-h light:dark cycle. Mice were given free access to water and group pair fed their respective diet. To do this, mice were initially given a weighed portion of food daily. If any mouse did not eat the entire portion of food, the weighed portion for all mice was decreased to the amount that the mouse ate the previous day. If all the mice consumed all of the diet, then the quantity of diet given was increased until an individual mouse did not consume all the food. By group feeding, we decreased the variability among the mice both within each diet group and among the diet groups. All mice were observed daily for clinical signs of disease, and body weight was recorded at wk 0 (start), 1, 2, 4, 6, 8, and 10 (end). At the end of study, mice were killed by CO2 asphyxiation and exanguination. All conditions and handling of the animals were approved by the Animal Care and Use Committee of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and conducted according to the NIH Guidelines for the Care and Use of Laboratory Animals.
Splenocyte isolation. Spleens were aseptically removed and placed in sterile RPMI 1640 (Biowhittaker) medium-supplemented with 25 mmol/L HEPES (Invitrogen Gibco), 2 mmol/L glutamine (Gibco), 100 kU/L penicillin and 100 mg/L streptomycin (Gibco). Medium, supplemented as described, was referred to as complete RPMI. Single cell suspensions were prepared as previously described (18). All the experiments were conducted under a condition of 37°C, atmosphere of 5% CO2, and a 95% humidity, unless indicated otherwise.
Cellular composition of splenocytes.
The percentages of major component cell types in spleen were determined using fluorescent-activated cell sorting (FACS)6 analysis. Splenocytes (1 x 106 cells/sample) were stained with following anti-mouse antibodies: FITC-conjugated anti-CD3 (T cells), PE-conjugated anti-CD19 (B cells), FITC-conjugated anti-CD4 [T helper (Th) cells], PE-conjugated anti-CD8 (T suppressor or cytotoxic cells), APC-conjugated anti-CD25 (IL-2 receptor chain), FITC-conjugated anti-natural killer-1.1 (NK-1.1 cells), and APC-conjugated anti-mouse F4/80 [macrophages (M
)]. F4/80 antibody was from Caltag and all the other antibodies were from BD PharMingen. Stained cells were analyzed on a FACSCalibur (BD Biosciences) and the results were analyzed using the Summit software, version 4.0 (DakoCytomation).
Natural killer cell activity assay. NK cell activity was assessed using radioisotope 51Cr release assay. YAC-1 cells, a murine lymphoma cell line purchased from ATCC, were incubated with 51Cr (Perkin Elmer Life and Analytical Sciences) (25 µCi/1 x 106 cells) for 90 min at 37°C. Labeled YAC-1 cells were added to appropriately diluted splenocytes in a round-bottomed 96-well plate (Nunc) for final effector:target cell ratios of 10:1, 25:1, 50:1, and 100:1. The cocultured cells were incubated in triplicate for 4 h at 37°C. Spontaneous release was measured as the amount of 51Cr released by target cells alone, and maximum release was measured by the amount of 51Cr released after the addition of 5% Triton X solution. Supernatant was collected after brief centrifugation (250 x g for 1 min) and counted in a Cobra II gamma counter (Packard Instruments) for radioactivity as counts per min (cpm). NK cell activity was expressed as a specific lysis percentage: (sample cpm – spontaneous cpm)/(maximum cpm – spontaneous cpm) x 100.
Mitogenic response of splenocytes. Splenocytes (1 x 105 cells/well), in 96-well, flat-bottom plates (Becton Dickinson Labware), were cultured in the presence or absence of the T cell mitogen concanavalin A (Con A; Sigma) at 0.5, 1.5, or 3 mg/L, phytohemagglutinin P (PHA; Difco Laboratories) at 2, 5, or 20 mg/L, or LPS (Sigma) at 0.1, 1, or 10 mg/L for 72 h. Cultures were pulsed with 0.5 µCi [3H]-thymidine (Perkin Elmer) during the final 4 h of incubation. The cells were harvested onto glass fiber filter mats (Wallac) by a Tomtec harvester (Wallac) and cell proliferation was quantified as the amount of [3H]-thymidine incorporated into DNA as determined by liquid-scintillation counting in a 1205 Betaplate counter (Wallac). The counter had an efficiency of >50% for 3H. Results are expressed as Bq.
Cytokine and prostaglandin E2 production by splenocytes.
Splenocytes (4 x 106 cells/well) in 24-well culture plates (Becton Dickinson Labware) were cultured in the presence of Con A (1.5 mg/L) or LPS (1 mg/L) for 24 h for inflammatory IL-6, tumor necrosis factor- (TNF), IL-12p70, and prostaglandin E2 (PGE2) production or in the presence of Con A (1.5 mg/L) or PHA (5 mg/L) for 48 h for IFN, IL-2, and IL-10 production. Cell-free supernatants were collected at the end of incubation and stored at –70°C for later analysis. All of the cytokines were measured using ELISA. The reagents for IL-6, TNF, IFN, IL-2, IL-10, and IL-12p70 assays were from BD PharMingen. PGE2 was measured using radioimmunoassay as previously described (19).
Cytokine, PGE2, NO, and H2O2 production by M.
Peritoneal exudate cells were obtained by peritoneal lavage and enriched for M using the method of Kumagai et al. (20). Peritoneal M prepared in this manner were at least 90% pure, as assessed by the expression of Mac-1 or F4/80 cell surface antibody.
M (5 x 105 cells/well) were incubated in 24-well culture plates (Becton Dickinson Labware) in the presence of LPS (1 mg/L) for 24 h. Cell-free supernatants were analyzed for cytokine, PGE2, and NO production. Cells were lysed in 1 mol/L NaOH for total cell protein analysis using the bicinchoninic acid protein assay kit (Pierce). IL-6, TNF, IL-12, and PGE2 were analyzed as described above and NO was measured using Griess assay as previously described (21). All the concentrations were normalized with total cell protein.
For measurement of H2O2 production, M (5 x 105 cells/well) were incubated in 96-well culture plates (Becton Dickinson Labware) in the presence of phorbol 12-myristate 13-acetate (Sigma) at 10 mg/L or zymosan (Sigma) at 1 g/L for 1 h. Supernatants were collected and analyzed for H2O2 production using Amplex Red hydrogen peroxide/peroxidase assay kit (Molecular Probes). Total cell protein was measured as described above and used to normalize H2O2 concentrations.
Statistical analysis.
All results were expressed as means ± SEM. Statistical analysis was conducted using Systat 10 statistical software. Significant differences were determined using ANOVA for overall effect of mushroom consumption and was followed by Fisher's least significance difference (LSD) post-hoc test for individual comparisons. Pearson correlation was used to determine associations between NK activity and production of IFN or TNF. Significance was set at P < 0.05.
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Results |
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TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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Subpopulations of splenocytes.
The percentage of total B cells (CD19+), total T cells (CD3+), Th cells (CD4+), suppressive/cytotoxic T cells (CD8+), regulatory T cells (CD4+/CD25+), NK cells (NK 1.1+), and M (F4/80+) did not differ among the 3 diet groups (data not shown).
NK cell activity. For all the effector:target cell ratios tested, NK cell activity was significantly enhanced by mushroom supplementation in a dose-dependent manner (Fig. 1). Similar results (data not shown) were obtained when NK activity was expressed as killing activity per given number of NK cells and calculated based on the total splenocytes used in this assay and the percentage of NK cells in the splenocytes obtained from the aforementioned FACS assay.
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was significantly greater in the group fed the 10% mushroom diet (25.9 ± 4.2 kU/L) than in the control group (16.5 ± 1.9 kU/L) and was intermediate in the 2% mushroom diet group (22.0 ± 2.9 kU/L). TNF production was significantly higher in the group fed the 10% mushroom diet (60 ± 18 ng/L) than in those fed the control diet (30 ± 5 ng/L). The 2% mushroom-fed mice tended to have higher (P = 0.09) IL-2 production compared with the control mice (data not shown). IL-10 (Th 2 cytokine), IL-12p70, IL-6, and PGE2 (lipid inflammatory mediator and T cell suppressor) production did not differ among diet groups (data not shown).
Correlations between NK activity and IFN and TNF production.
Con A- (Fig. 2A) and PHA-stimulated (Fig. 2B) IFN production and NK activity in splenocytes were significantly and positively correlated. In addition, NK activity and TNF levels were weakly but significantly correlated (Fig. 2C). The results in Figure 2 were obtained at a 100:1 effector:target cell ratio; results were similar at all the other effector:target cell ratios tested (data not shown).
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secretion of inflammatory mediators and H2O2.
Mushroom supplementation did not affect peritoneal M production of IL-6, TNF, PGE2, NO, and H2O2 (data not shown), suggesting that macrophage-derived products do not contribute to the mushroom-induced enhancement of NK activity. T and B cell proliferation. Mushroom supplementation did not affect the proliferative response of splenocytes upon stimulation with T cell mitogen Con A or PHA, or B cell mitogen LPS (Fig. 3).
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Discussion |
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TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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and TNF production. The results suggest that the consumption of white button mushrooms, a strain constituting 90% of mushrooms consumed in the U.S., can modulate the body's innate immunity. To our knowledge, for the first time, these results demonstrate that dietary supplementation with white button mushrooms significantly enhances the ability of spleen NK cells to lyse the target tumor cells in a dose-dependent manner. This increased NK capacity mainly represents a more vigorous cytolytic activity of NK cells toward target cells and is not due to an increase in the number of total NK cells because the percentage of NK cells in the spleen was not altered by mushroom supplementation. Other strains of edible mushrooms have also been shown to increase NK activity; however, these studies were mostly conducted in tumor-bearing or virus-infected animals (15,22–24).
NK cells are a group of specialized lymphocytes characterized by their ability to spontaneously kill pathogen-infected cells and tumor cells and are thus a key component of the innate immune system (25). This function of NK cells is mediated and regulated by the immunoregulatory cytokines produced by NK cells themselves as well as other cells such as T cells and M. IFN is the most important cytokine in mediating NK activity. IFN is thought to play an essential role in NK cell-mediated suppression of viral and bacterial infection (26–28) and the inhibition of tumor initiation and metastasis (26,29). To a lesser degree, TNF may also contribute to the antiviral and antitumor effects of NK cells (26,28). In this study, the enhancement of NK activity by mushroom supplementation was accompanied by an increase in splenocyte production of IFN. Furthermore, there were significant positive correlations between NK activity and IFN production. We also found a higher TNF production, but only in mice fed 10% mushroom and when compared with controls. Accordingly, a weak but significant correlation was found between NK activity and TNF production. These results are consistent with a previous study in which i.p. injection of D-Fraction extracted from maitake mushroom increased IFN and TNF production by whole spleen cells in carcinoma-bearing C3H/HeN mice (24). Because IFN and TNF are produced by different cell types found in spleen (T cells, NK cells, and M), further studies using intracellular cytokine staining and flow cytometry are needed to determine the cellular origin of the mushroom-induced increase in these cytokines. Our results using peritoneal macrophages, however, indicate that the effect of mushroom is not mediated through M.
Helper T cells are designated as Th 1 and Th 2 subpopulations based on the patterns of their cytokine secretion. Th 1 cells, characterized by IL-2, IFN, and TNF production, are mainly involved in cell-mediated immunity to intracellular infections. Th 2 cells, characterized by IL-4, IL-5, and IL-10 production, are mainly involved in humoral immunity against extracellular infections. Mushroom polysaccharides have been shown to induce polarization of Th response but with a varied manner. Although some of these mushroom-derived compounds induce Th 1 response, others favor Th 2 response. It has been suggested that the effect of mushrooms on Th cell polarization is dependent upon the type of the mushroom-derived polysaccharides and animal strain used (7). In this study, mushroom supplementation increased IFN and TNF production and tended to increase in IL-2 production, but did not affect IL-10 production. These results indicate that white button mushrooms may induce a shift toward Th 1 response. This is further supported by our in vitro experiment in which extract of white button mushroom promoted maturation and the antigen-presenting function of bone marrow-derived dendritic cells (Z. Ren, Z. Guo, S. N. Meydani, and D. Wu, unpublished results), which have been shown to induce Th 1 response (30,31). Whereas enhanced Th 1 response is beneficial for antimicrobial and antitumor defense, it may be undesirable in certain autoimmune and inflammatory disorders where overactive Th 1 response plays a role. Thus, further studies using appropriate animal models are needed to determine the clinical significance of the observed immunomodulatory effects of white button mushrooms.
The polysaccharides, particularly ß-1,3-glucans, are believed to be the active components in mushrooms and are therefore most frequently used in the studies to determine the effect of mushrooms. It is still not well understood how polysaccharides affect systemic immune function after oral ingestion given the fact that they are dietary fibers. However, several studies have, indeed, observed a tumor-inhibitory effect after oral administration of certain glucans (16,24,32–34). We previously reported that feeding mice a diet containing extract of the mycelia of Coriolus versicolor increased delayed-type hypersensitivity skin response, an in vivo measure of cell-mediated immunity, in old mice (18). Together with the findings of our dietary supplementation study, it is reasonable to suggest that, in contrast to common thought, immunomodulatory effects of mushrooms may not entirely depend on the distribution of these polysaccharides into the target tissues. Alternatively, because the cells (dendritic cells, M, lymphocytes) in gut-associated lymphoid tissues have direct access to gut content and continuously recirculate in the blood and lymphatic systems, they can be activated by mushroom polysaccharides in the gut and move to blood and other systemic immune organs. It is also possible that when whole mushroom extracts are used, some nonpolysaccharide molecules present in mushrooms, such as lipids, vitamins, flavonoids, minerals, and trace elements, with the immunomodulating property might contribute to the observed effects. However, the 2 and 10% mushroom powder added to the diets in this study do not substantially increase the level of nutrients that are known to have immunostimulatory effects above those present in the basal AIN-93M diet. For example, based on the food intake of mice and nutrient composition of raw white button mushrooms (35), we calculated that the 2 and 10% mushroom powder in diets provided only 2.4 and 12% of more zinc and 7 and 35% more selenium than those found in the basal diet, respectively. Therefore, it seems unlikely that the nonpolysaccharide nutrients present in mushrooms play a major role in inducing the enhancement of NK activity following mushroom consumption.
In conclusion, the results of this study demonstrate that dietary supplementation with white button mushrooms enhances NK cell activity. This effect of mushrooms may be mediated through increased production of IFN and TNF. These results suggest that consumption of white button mushrooms may increase innate immunity to tumors and viral infections. Future studies are needed to determine the clinical significance of these findings, particularly in those with impaired immune functions, such as elderly, and in those with cancer.
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FOOTNOTES |
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2 Author disclosures: D. Wu, M. Pae, Z. Ren, Z. Guo, D. Smith, and S. N. Meydani, no conflicts of interest.
6 Abbreviations used: Con A, concanavalin A; cpm, counts per minute; FACS, fluorescent-activated cell sorting; M, macrophages; NK, natural killer; PGE2, prostaglandin E2; PHA, phytohemagglutinin; Th, helper T cells; TNF, tumor necrosis factor-.
Manuscript received 8 February 2007. Initial review completed 5 March 2007. Revision accepted 3 April 2007.
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LITERATURE CITED |
|---|
|
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1. Bancroft GJ. The role of natural killer cells in innate resistance to infection. Curr Opin Immunol. 1993;5:503–10.[Medline]
2. Biron CA, Brossay L. NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol. 2001;13:458–64.[Medline]
3. Brown DM, Roman E, Swain SL. CD4 T cell responses to influenza infection. Semin Immunol. 2004;16:171–7.[Medline]
4. Wong P, Pamer EG. CD8 T cell responses to infectious pathogens. Annu Rev Immunol. 2003;21:29–70.[Medline]
5. Belardelli F, Ferrantini M. Cytokines as a link between innate and adaptive antitumor immunity. Trends Immunol. 2002;23:201–8.[Medline]
6. Diefenbach A, Raulet DH. The innate immune response to tumors and its role in the induction of T-cell immunity. Immunol Rev. 2002;188:9–21.[Medline]
7. Borchers AT, Keen CL, Gershwin ME. Mushrooms, tumors, and immunity: an update. Exp Biol Med (Maywood). 2004;229:393–406.
8. Borchers AT, Stern JS, Hackman RM, Keen CL, Gershwin ME. Mushrooms, tumors, and immunity. Proc Soc Exp Biol Med. 1999;221:281–93.[Abstract]
9. Jong SC, Birmingham JM. Medicinal and therapeutic value of the shiitake mushroom. Adv Appl Microbiol. 1993;39:153–84.[Medline]
10. Lull C, Wichers HJ, Savelkoul HF. Antiinflammatory and immunomodulating properties of fungal metabolites. Mediators Inflamm. 2005;2005:63–80.[Medline]
11. Maeda YY, Chihara G. Lentinan, a new immuno-accelerator of cell-mediated responses. Nature. 1971;229:634.[Medline]
12. Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol. 2002;60:258–74.[Medline]
13. Sullivan R, Smith JE, Rowan NJ. Medicinal mushrooms and cancer therapy: translating a traditional practice into Western medicine. Perspect Biol Med. 2006;49:159–70.[Medline]
14. Ooi VE, Liu F. Immunomodulation and anti-cancer activity of polysaccharide-protein complexes. Curr Med Chem. 2000;7:715–29.[Medline]
15. Kurashige S, Akuzawa Y, Endo F. Effects of Lentinus edodes, Grifola frondosa and Pleurotus ostreatus administration on cancer outbreak, and activities of macrophages and lymphocytes in mice treated with a carcinogen, N-butyl-N-butanolnitrosoamine. Immunopharmacol Immunotoxicol. 1997;19:175–83.[Medline]
16. Ng ML, Yap AT. Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus edodes). J Altern Complement Med. 2002;8:581–9.[Medline]
17. Reeves PG, Nielsen FH, Fahey GC, Jr. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr. 1993;123:1939–51.
18. Wu D, Han SN, Bronson RT, Smith DE, Meydani SN. Dietary supplementation with mushroom-derived protein-bound glucan does not enhance immune function in young and old mice. J Nutr. 1998;128:193–7.
19. Hayek MG, Meydani SN, Meydani M, Blumberg JB. Age differences in eicosanoid production of mouse splenocytes: effects on mitogen-induced T-cell proliferation. J Gerontol. 1994;49:B197–207.[Medline]
20. Kumagai K, Itoh K, Hinuma S, Tada M. Pretreatment of plastic petri dishes with fetal calf serum. A simple method for macrophage isolation. J Immunol Methods. 1979;29:17–25.[Medline]
21. Misko TP, Schilling RJ, Salvemini D, Moore WM, Currie MG. A fluorometric assay for the measurement of nitrite in biological samples. Anal Biochem. 1993;214:11–6.[Medline]
22. Arinaga S, Karimine N, Takamuku K, Nanbara S, Inoue H, Nagamatsu M, Ueo H, Akiyoshi T. Enhanced induction of lymphokine-activated killer activity after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol. 1992;14:535–9.[Medline]
23. Kaneko Y, Chihara G., eds. Potentiation of host resistance against microbial infections by lentinan and its related polysaccharides. New York: Plenum; 1992.
24. Kodama N, Komuta K, Sakai N, Nanba H. Effects of D-Fraction, a polysaccharide from Grifola frondosa on tumor growth involve activation of NK cells. Biol Pharm Bull. 2002;25:1647–50.[Medline]
25. Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376.[Medline]
26. Papamichail M, Perez SA, Gritzapis AD, Baxevanis CN. Natural killer lymphocytes: biology, development, and function. Cancer Immunol Immunother. 2004;53:176–86.[Medline]
27. Lodoen MB, Lanier LL. Natural killer cells as an initial defense against pathogens. Curr Opin Immunol. 2006;18:391–8.[Medline]
28. Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol. 1999;17:189–220.[Medline]
29. Street SE, Cretney E, Smyth MJ. Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood. 2001;97:192–7.
30. Harada N, Kodama N, Nanba H. Relationship between dendritic cells and the D-fraction-induced Th-1 dominant response in BALB/c tumor-bearing mice. Cancer Lett. 2003;192:181–7.[Medline]
31. Kodama N, Harada N, Nanba H. A polysaccharide, extract from Grifola frondosa, induces Th-1 dominant responses in carcinoma-bearing BALB/c mice. Jpn J Pharmacol. 2002;90:357–60.[Medline]
32. Yunoki S, Tanaka N, Hizuta A, Orita K. Enhancement of antitumor cytotoxicity of hepatic lymphocytes by oral administration of PSK. Int J Immunopharmacol. 1994;16:123–30.[Medline]
33. Sabolovic D, Galoppin L. Effect of a protein bound polysaccharide (PS-K) on tumor development and infections in splenectomized rats and mice. Int J Immunopharmacol. 1986;8:41–6.[Medline]
34. Tsang KW, Lam CL, Yan C, Mak JC, Ooi GC, Ho JC, Lam B, Man R, Sham JS, Lam WK. Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer. Respir Med. 2003;97:618–24.[Medline]
35. Nutrient Data Laboratory [homepage on the internet]. USDA national nutrient database for standard reference, release 19 [updated Sept. 2006; cited 2007 Feb 5] Available from: http://www.ars.usda.gov/ba/bhnrc/ndl.
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