ABD活性因子与免疫系统相关研究.doc

美源康富A.B.D活性因子与免疫系统相关研究美源康富ABD活性因子为免疫细胞提供“食粮”，增强免疫反应美源康富ABD活性因子临床证明能够促进健康人体白细胞合成更多谷胱甘肽，为白细胞的分化和增生提供“食粮”，促进B细胞产生抗体，增加杀手T细胞的杀伤力，明天提高各项免疫指标。美源康富ABD活性因子中和自由基，修复炎症损伤免疫反应过程中，白细胞会产生大量过氧化物去消灭抗原。这些过氧化物当然也会伤害周围正常的组合和细胞，包括免疫细胞本身。美源康富ABD活性因子临床证明能够促进人体所有细胞合成更多谷胱甘肽，谷胱甘肽是细胞的“抗氧化剂之王”，能快速中和炎症反应中产生的大量自由基，将炎症对正常组织的损伤降到最低，加速人体的自愈过程。美源康富ABD活性因子抗炎镇痛过度的炎症反应对人体的伤害有时候比益处更大，比如慢性炎症和通风，炎症最终成了疾病的症状，带来无法忍受的疼痛。美源康富ABD活性因子调节前列腺素的合成，抑制COXII的活性，从而达到消炎镇痛的效果。1. Influence of Dietary Lactalbumin Hydrolysate on the Immune System of Mice and Resistance to SalmonellosisG. Bounous, M.M. Stevenson*, P.A.L. KongshavnCentre hospitalier universitaire, Sherbrooke, Quebec, Canada; *Montreal General Hospital Research Institute and McGill University, Montreal, Quebec, CanadaTHE JOURNAL OF INFECTIOUS DISEASES, 144: 281, 1981Abstract: In the present study we investigated the effect of four weeks of treatment with a diet containing lactalbumin hydrolysate (LAH: Nestlé, Vevey, Switzerland) on the immune response of C3H/HeN mice. Our data indicate that it was possible to increase the level of this type of protein in the diet above the minimum requirement (12% LAH) and thus produce augmented humoral immune responsiveness and resistance to salmonellosis.Lactalbumin = Whey Protein Concentrate研究主题使用美源康富ABD活性因子对小鼠免疫系统和抗沙门氏感染能力的影响研究目的本实验是为了研究向C3H/HeN小鼠喂食美源康富ABD活性因子4周后，对其免疫系统的影响。研究结果我们数据表明，提高饲料中ABD活性因子的含量，能够影响体液免疫反应和抵抗沙门氏感染的能力。表1 使用4种不同配方的蛋白喂食C3H/HeN小鼠4周后，对小鼠注射沙门氏菌，检测小鼠的免疫反应指标以及存活率。如表所示，用沙门氏菌免疫接种后，各蛋白饲料组的小鼠脾脏重量都有所增加，证实了脾脏在接种后的免疫反应。斑块生成细胞的数量在食用20%和28%ABD活性因子时比其它两组明显增加；各蛋白组的吞噬细胞数量在接种后都 远大于未接种时，20%ABD活性因子组的吞噬细胞数量大于其他三组。12%ABD活性因子 组的小鼠存活率高于普通蛋白组，当ABD活性因子含量增加为28%时，存活率提升现象更 明显。说明ABD活性因子有增强免疫力的效果，这种效果与食用浓度有关。免疫反应指标22%普通蛋白组12% ABD20% ABD28% ABD脾脏重量/体重%（接种）55.2±2.048.0±1.650.2±254.4±2.6脾脏重量/体重%（未接种）37.5±0.941.1±2.449.9±1.850.6±0.6斑块生成细胞数量94±10.059±5.1155±9.2159±11.9吞噬细胞数量（接种）12350±64811189±1851399±50912094±198吞噬细胞数量（未接种）627±10400±30621±181595±767天存活率%0100010014天存活率%03006021天存活率%0707文献来源 G. Bounous, M.M. Stevenson, P.A.L. Kongshavn，传染病期刊，1981年114期281页。 2. Influence of Dietary Protein Type on the Immune System of MiceG. Bounous, L. Létourneau and P.A.L. KongshavnCentre hospitalier universitaire, Sherbrooke, Quebec, Canada; J1H 5N4 and Montreal General Hospital Research Institute and Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6J. NUTR. 113: 1415-1421, 1983Abstract: The effect of graded amounts of dietary lactalbumin (L), casein (C), soy (S), wheat (W) protein and Purina rodent chow (stock diet) on the immune responsiveness of C3H/HeN mice has been investigated by measuring the specific humoral immune response to sheep red blood cells (SRBC), and horse red blood cells (HRBC) as well as the nonspecific splenic cell responsiveness to phyto-hemagglutinin (PHA) and concanavalin A (Con A) after stimulation with Myco-bacterium bovis, strain BCG.  The nutritional efficiency of these diets was normal and similar.  The immune response of mice fed the L diets, was found to be almost five times higher than that of mice fed the corresponding C diets.  The humoral immune response of mice fed C, S, and W diets was substantially lower than that of mice fed stock diet, whereas that of mice fed L diet was higher.  The above-described immune effect of all tested proteins was obtained at 20 g/100 g concentration with no further increments with 30- and 40 g/100 g protein in the diet.  Mitogen responsiveness to PHA and Con A in L diet-fed mice was only slightly higher than that of C diet-fed mice.  Little difference in immune responses was noted among mice fed C, S or W protein diets.  The principal factor responsible for the observed immune effect does not appear to be the availability or concentration of single essential amino acids but rather the composite effect of the specific amino acid distribution in the protein.研究主题服用美源康富ABD活性因子对小鼠免疫系统的影响研究内容选用C3H/HeN小鼠，分别喂食含20%乳白蛋白、酪蛋白、大豆蛋白和小麦蛋白饲料和普通饲料，检测小鼠对羊血红细胞和马血红细胞的特 定免疫反应，以及肉毒杆菌刺激的脾细胞对植物凝聚素（PHA）和伴刀 豆球蛋白A（ConA）的非特异反应。不同饲料的营养成分相似。研究结果ABD活性因子组所有小鼠的免疫反应比酪蛋白组高近乎5倍，体液免疫反应比普通饲料组高，而其它三组的体液免疫反应比普通饲料组低。以上反应是在蛋白含量20%情况下观察到的，当含量增加到30%和40%时，反应没有进一步增强。ABD活性因子组的有丝分裂素对PHA和ConA的反应比 酪蛋白组稍高。酪蛋白组、大豆蛋白组和小麦蛋白组的免疫反应几乎无差别。每个脾脏的血小板生成细胞数量LLLLCCCC图1 分别选用两种不同品系的小鼠，用酪蛋白（C）、12%和28%浓度的ABD活性因子（L）饲料喂食4周，绵羊红细胞刺激小鼠脾脏产生免疫反应，检测小鼠脾脏斑块生成细胞（PFC）的数量。ABD活性因子组的PFC数量明显高于酪蛋白组，这一现象在浓度28%时更显著。研究结论这种对免疫力的影响似乎不是某种单一氨基酸的作用，而是几种特定氨基酸在蛋白中的分布造成的。文献来源 G. Bounous, L. Létourneau and P.A.L. Kongshavn ，营养学期刊，1983年113期1415-1421页。 3. Mechanism of Altered B-Cell Response Induced By Changes in Dietary Protein Type in MiceG. Bounous, N. Shenouda,1 P.A.L. Kongshavn2 and D.G. Osmond1Department of Surgery, Centre Hospitalier Universitaire, Sherbrooke, Quebec, Canada, J1H 5N4; 1Department of Anatomy, McGill University, Montreal, Quebec, Canada, H3A 2B2; and 2Department of Physiology, McGill University, Montreal, Quebec, Canada, H3A 2B2J. NUTR. 115: 1409-1417, 1985Abstract: The effect of 20 g/100 g dietary lactalbumin (L) or casein (C) diets or a nonpurified (NP) diet on the immune responsiveness of C57B1/6J, C3H/HeJ and BALB/cJ mice has been investigated by measuring the response to the T cell-independent antigen, TNP-Ficoll.  To investigate the possible influence of dietary protein type on the supply of B lymphocytes, bone marrow lymphocyte production has been examined by a radioautographic assay of small lymphocyte renewal and an immuno-fluorescent stathmokinetic assay of pre-B cells and their proliferation.  The humoral response of all mice fed the L diet was found to be higher than that of mice fed the C diet or non purified diet.  A similar pattern of dietary protein effect in (CBA/N x DBA/2J) F1 mice carrying the xid defect was observed following challenge with sheep red blood cells (SRBC).  An even greater enhancing effect of dietary L was noted in normal (DBA/2J x CBA/N) F1 mice after immunization with SRBC, but in contrast, the normal large-scale production of B lymphocytes in mouse bone marrow was independent of the type of dietary protein.  Dietary protein type did not affect blood level of minerals and trace metals.  The free plasma amino acid profile essentially conformed to the amino acid composition of the ingested protein, suggesting that the changes in plasma amino acid profile might be a crucial factor in diet-dependent enhancement or depression of the B-cell response.  The findings indicate that the observed effects of altered dietary protein type on humoral immune responsiveness are not exerted centrally on the rate of primary B-lymphocyte production in the bone marrow, but may reflect changes either in the functional responsiveness of the B lymphocytes themselves or in the processes leading to their activation and differentiation in the peripheral lymphoid tissues.研究主题调整食用蛋白种类而改变老鼠B细胞反应的机制研究内容选用三种不同品系的小鼠，分别喂食含20%ABD活性因子、酪蛋白和未纯化蛋白饲料，检测T细胞依赖抗原TNP-Ficoll来衡量其免疫反应， 用对小淋巴细胞更新的放射成像分析来检测骨髓淋巴细胞制造，用免疫 荧光细胞分裂速度分析检测B细胞增殖，从而衡量不同蛋白食品对B细 胞反应的作用。研究结果ABD活性因子组所有小鼠的体液免疫反应高于其他两组。相似的现象在xid缺陷的F1小鼠上也被观察到，这样的现象在正常F1小鼠身上更加明显。小鼠骨髓中的B细胞生成并不受食用蛋白的影响。食用蛋白对 血液中的矿物质和金属含量无影响。血浆游离氨基酸检测确认了食用的蛋白成分在血液中出现，说明这些氨基酸成分与B细胞反应增强有关。三硝基甲苯聚蔗糖每个脾脏的血小板生成细胞数量图1 选用三种不同品系的小鼠C57Bl/6J,C3H/HeJ和BALB/cJ，对三硝基甲苯聚蔗糖产生免疫反应后，检测小鼠脾脏生成免疫斑块细胞（PFC）数量。小鼠进行了2周的饮食处理，分别使用了20g/100gABD活性因子（L），酪蛋白（C）（20g/100g）以及没有提纯的食物（NP）喂食。每一个数值代表了平均值±标准差，n=10只小鼠。通过学生的t检验，L对C，L对N和NP对C:P<0.025。有图可见，ABD活性因子组小鼠的免疫反应明显高于其他两组，三种小鼠的结果相同。图2 检测F1基因缺陷的CBDBA/2J小鼠（A）以及F1基因正常的CBDBA/2J小鼠在注射绵羊红细胞，脾脏生成斑块细胞（PFC）数量。小鼠都进行了2周饮食处理，分别使用了20g/100gABD活性因子（L）,酪蛋白（C）（20g/100g）以及没有提纯的食物（NP）喂 食。每一个数值代表了平均值±标准差，n=10。通过学生t检验，108数量级羊红血细胞F1有缺陷的小鼠，L对C，P<0.005。F1正常的老鼠：L对C,L对NP和NP对C，P<0.0005。5×108数 量级羊红血细胞情况下，L对C，L对NP和NP对C：P<0.025。有图可见，F1缺陷小鼠的免疫反应被ABD活性因子增强，尤其是当抗原浓度提高的时候；这样的增强反应在F1正常小鼠 身上更为明显，说明这与蛋白的合成有关，因为F1基因参与蛋白的合成。研究结论不同的蛋白食品对体液免疫的改变，不会影响骨髓B淋巴母细胞的产生，却会影响B细胞自身的反应和周围淋巴组织中B细胞的激活。文献来源 G. Bounous, N. Shenouda, P.A.L. Kongshavn and D.G. Osmond，营养学期刊，1985年115期1409-1417页。 4. The Immunoenhancing Property of Dietary Whey Protein ConcentrateGustavo Bounous1,2, Patricia A.L. Kongshavn1,3 and Phil Gold1,41The Montreal General Hospital Research Institute, 2Departments of Surgery, 3Physiology, 4Medicine, McGill University, Montreal, QuebecCLINICAL AND INVESTIGATIVE MEDICINE, VOL. 11,.NO. 4,.PP 271-278,. 1988. (ORIGINAL MANUSCRIPT SUBMITTED OCTOBER 22, 1987: ACCEPTED IN REVISED FORM JANUARY  25, 1988)Abstract: The plaque-forming cell response to sheep red blood cells was found to be enhanced in mice fed a formula diet containing 20 g lactalbumin /100 g diet in comparison to mice fed equivalent formula diets of similar nutritional efficiency containing 20 g / 100 g diet of either casein, soy, wheat or corn protein, egg albumin, beef or fish protein, Spirulina maxima, or Scenedesmus protein, or Purina mouse chow. This effect was manifest after 2 weeks and persisted for at least 8 weeks of dietary treatment. Mixing lactalbumin with either casein or soy protein in a 20 g protein / 100 g diet formula significantly enhanced the immune response in comparison to that of mice fed diets containing 20% soy protein or casein.研究主题食用美源康富ABD活性因子有增强免疫力的特性研究综述食用含20%美源康富ABD活性因子饲料的小鼠，对羊血红细胞的免 疫反应明显高于使用同样配比的含其他蛋白的饲料组，包括酪蛋白、大豆蛋白、小麦或玉米蛋白、鸡蛋白蛋白、牛肉或鱼肉蛋白、螺旋藻蛋白、栅藻和普通小鼠饲料。这一过程从服用两周后开始出现，持续到第八周服用结束。在酪蛋白和大豆蛋白中掺入ABD活性因子，与单独食用酪蛋白或大豆蛋白相比，小鼠的免疫力增强。不同蛋白饲料对小鼠免疫力的影响图1 喂食小鼠不同蛋白成分的饲料8周，用绵羊红细胞刺激，检测斑块生成细胞（PFC）数量，L：ABD活性因子，C：酪蛋白，Sp：螺旋藻蛋白，S：大豆蛋白，W： 小麦蛋白，Sc：栅藻蛋白，Co：玉米蛋白，E：鸡蛋白蛋白，B：牛肉蛋白，F：鱼肉蛋 白，P：Purina鼠粮，L/S：ABD活性因子+大豆蛋白，L/C：ABD活性因子+酪蛋白。如图显 示，各种蛋白饲料中，只有ABD活性因子有明显增强小鼠免疫力的作用，当在大豆蛋白中掺入一半ABD活性因子，或者是在酪蛋白中掺入ABD活性因子后，也有免疫增强作用。文献来源 Gustavo Bounous, Patricia A.L. Kongshavn1 and Phil Gold，临床医学研究，1988年11期271-278页。5. Immunoenhancing Property of Dietary Whey Protein in Mice: Role of GlutathioneG. Bounous, G. Batist, P. GoldMontreal General Hospital, QuebecCLIN INVEST MED, 12: 154-61, 1989Abstract: The spleen cells immune response to sheep red blood cells of C3H/HeJ mice fed a 20 g whey protein/100 g diet is substantially higher than that of mice fed an equivalent casein diet of similar nutritional efficiency.  The present study indicates that the observed immunoenhancing effect of the whey protein mixture is dependent on the overall amino acid pattern resulting from the contribution of all its protein components.  Whey protein contains substantially more cysteine than casein.  Dietary cysteine is considered to be a rate limiting substrate for the synthesis of glutathione which is necessary for lymphocyte proliferation.  Our studies show that enhancement of host humoral immune response is associated with greater and more sustained production of splenic glutathione during the antigen driven clonal expansion of the lymphocyte in whey protein fed mice in comparison to mice fed the equivalent casein or the cysteine-enriched casein diet.  Hence the efficiency of dietary cysteine in inducing supernormal glutathione levels is greater when it is delivered in the whey protein than as free cysteine.  Administration of S-(n-butyl) homocysteine sulfoximine, which reduces splenic glutathione level by half, produces  a 4-5 fold drop in the humoral immune response of whey protein diet-fed mice.  This is further evidence of the important role of glutathione in the immunoenhancing effect of dietary whey protein.研究主题美源康富ABD活性因子增强小鼠免疫力：谷胱甘肽的作用研究综述食用含20%美源康富ABD活性因子饲料的小鼠，其脾脏细胞对羊血红细胞的免疫反应明显高于使用同样配比的酪蛋白饲料组。我们的研究显示，ABD活性因子增强免疫的功能与其中蛋白元素的氨基酸序列有 关。ABD活性因子含有比酪蛋白中丰富的半胱氨酸。谷胱甘肽是淋巴细 胞增殖的必需物质，食物中的半胱氨酸是合成谷胱甘肽的限定性因素。 我们研究显示，食用ABD活性因子饲料的小鼠体液免疫反应强于食用酪蛋白饲料或含有半胱氨酸的酪蛋白饲料，与这些小鼠在抗原驱使的淋巴 细胞扩增过程中，脾脏谷胱甘肽的合成更多有关。由此说明，补充半胱 氨酸提升谷胱甘肽水平，要用乳清蛋白的形式输送，而不是直接补充游离的半胱氨酸。使用半胱氨酸同源物硫亚胺，能使脾脏谷胱甘肽减半， 使食用ABD活性因子饲料的小鼠的体液免疫降低4到5倍。这进一步证明了ABD活性因子增强免疫力的作用与提升谷胱甘肽有关。图1图1小鼠分为三组，分别喂食20g/100gABD活性因子（WPC）、酪蛋白（C）或者酪蛋白与半胱氨酸（C+Cys）各三周。在对106单位绵羊红细胞产生免疫反应后的第3、4、5、6天，检测小鼠脾脏生成免疫斑块的细胞数量。每个数值为平均值±标准差。有图看 见，注射绵羊红细胞后第4天，小鼠开始产生免疫反应，ABD活性因子组的免疫反应远远高于其他两组。酪蛋白组和酪蛋白+半胱氨酸组之间的免疫反应无差别，说明补充游离性半胱氨酸不能增强免疫反应。图2分别给小鼠喂食20g/100g ABD活性因子（WPC）、酪蛋白（C）、乳清蛋白水解物、酪蛋白水解物、乳清蛋白氨基酸等同物（WPC.a.a）、酪蛋白氨基酸等同物（C.a.a）、-乳球蛋白（L）、-乳白蛋白（L）、-球蛋白（G）或者牛血清蛋白（SA） 三周，比较各种成分对小鼠免疫反应的影响。在对106单位绵羊红细胞产生免疫反应峰值 的当天，检测小鼠脾脏产生的免疫斑块细胞数量。每个数值为平均值±标准差。由图可见，ABD活性因子、水解ABD活性因子和ABD活性因子同样氨基酸成分的蛋白都有明显增强小鼠免疫力的效果，而酪蛋白、水解酪蛋白和酪蛋白成分氨基酸没有这样的效果。单独 提取ABD活性因子中的蛋白成分-乳球蛋白（L）、-乳白蛋白（L）、-球蛋白（G）和牛血清蛋白（SA），发现这几种蛋白单独作用，也能提升小鼠免疫力。说明ABD活性因子中有效提升免疫力的成分是这几种蛋白。图3 喂食未免疫的小鼠相关食物后，以百分比（%）显示的其脾脏谷胱甘肽水平。三周内喂食20g/100g ABD活性因子（WPC）、酪蛋白（C）、或者酪蛋白与半胱氨酸（C+Cys）。D代表对5×106单位绵羊红细胞（SRBC）产生免疫反应的天数。每个数值为10只小鼠平 均值±标准差。如图显示，ABD活性因子组的小鼠脾脏谷胱甘肽含量从2-6天都有明显提升；而酪蛋白组小鼠脾脏的谷胱甘肽含量比之前有所下降；酪蛋白+半胱氨酸组小鼠的脾脏谷胱甘肽含量不稳定，无明显提升效果。图4 左：左：喂食小鼠20g/100gABD活性因子（WPC）、乳清蛋白提纯物+丁硫氨酸-亚砜亚胺（WPC+BSO）、酪蛋白（C）三种，在对106单位绵羊红细胞产生免疫反应峰值 当天，检测小鼠脾脏生成血小板的细胞数量。每个数值为平均值±标准差：ABD活性因 子对比ABD活性因子+BSO或者酪蛋白：P<0.0005。右：在同一时间检测小鼠脾脏的谷胱 甘肽含量。每个数值为平均值±标准差：ABD活性因子对ABD活性因子+BSO或者酪蛋 白：P<0.0005。有图可见，ABD活性因子提升谷胱甘肽、增强免疫反应的功能再一次被验 证，酪蛋白无此功能；当使用BSO阻断半胱氨酸合成谷胱甘肽的通路后，ABD活性因子的 这种增强作用被消除。说明ABD活性因子提升谷胱甘肽、增强免疫反应的功能是靠其中的 非游离半胱氨酸成分合成谷胱甘肽来实现的。文献来源 G. Bounous, G. Batist, P. Gold，临床医学研究，1989年12期154-161页。6. Changes in Biliary Secretory Immunoglobulins A in Mice Fed Whey ProteinsCostantino AM, Balzola F, Bounous G.MINERVA DIETOL GASTROENTEROL 35(4): 241-5, 1989A whey protein diet has been shown to enhance splenic immune response to sheep red blood cells (SBRC) in mice.  This study was designed to investigate the influence of the type of dietary protein on the biliary secretory IgA.  A/J mice were fed defined formula diets containing either 20% whey protein, or 20% casein.  Another group was fed Purina mouse chow.  After 3 weeks of dietary treatment the body weight of each mouse was recorded and the gall-bladder was removed and its whole content analyzed by ELISA to determine S-IgA secretion.  Body weight curves were similar in all dietary groups; higher biliary levels of S-IgA appeared in the whey protein fed mice than in the casein (p less than 0.025) or purine (p less than 0.025) fed mice.  Dietary protein type may have a direct influence on the immune response in the gastrointestinal tract, without affecting body weight.研究主题食用美源康富ABD活性因子的小鼠胆囊分泌免疫球蛋白A的变化研究目的一种乳清蛋白饲料（ABD活性因子）被证实能增加小鼠脾脏对羊血红细胞的免疫反应。本实验是为了研究这种蛋白对胆囊分泌IgA的影响。研究内容选用A/J小鼠，分别喂食含20%ABD活性因子、酪蛋白饲料，以及普通饲料，喂养三周后，测量各组小鼠的体重，去其胆囊组织做ELISA分析，测定其中S-IgA含量。 研究结果体重曲线三组无差异，ABD活性因子组的S-IgA含量高于其他两组。研究结论使用蛋白种类对胃肠道免疫反应有直接影响，却不会影响体重。文献来源 Costantino AM, Balzola F, Bounous G， 膳食胃肠道学期刊，1989年35期4卷241-245页。