Effects of handling during infancy on the sympathetic–adrenal medullary system of rats

We examined the effects of daily handling and maternal separation (5 min per day) on the responsiveness of the sympathetic-adrenal medullary system of Sprague-Dawley rats before weaning and in adulthood. Plasma levels of norepinephrine (derived primarily from sympathetic nerves) and epinephrine (released from the adrenal medulla) were elevated in handled pups compared to unhandled controls at 14 and 18 days of age but not at 6 and 10 days of age. When tested in adulthood, previously handled and control rats did not differ with respect to basal or stress-induced increments in plasma levels of norepinephrine and epinephrine. These results indicate that brief daily episodes of handling and maternal separation are attended by an increase in sympathetic-adrenal medullary tone in 14–18-day-old rats. However, the enhanced response of the sympathetic–adrenal medullary system of separated rats may not persist into adulthood.     

Aire 对巨噬细胞极化影响的研究

目的:研究自身免疫调节因子(Aire)对巨噬细胞极化的影响。方法:分别用LPS、IL-4 以及LPS 联合免疫复合物刺激小鼠单核巨噬细胞系RAW264郾7 细胞、稳定表达GFP-Aire 的RAW264.7 细胞(A33-3) 细胞和稳定表达GFP 的RAW264.7 细胞(C1-6),使其向M1(LPS)、M2a(IL-4)和M2b(LPS 联合免疫复合物)型巨噬细胞极化。通过Real-time PCR 检测各组细胞中M1 型巨噬细胞特征分子IL-1、iNOS 和IL-6,M2a 型特征分子Arg-1 和M2b 型特征分子IL-10 的表达水平,研究Aire 对各种类型巨噬细胞极化的影响。结果:LPS 在0.5 g/ ml 浓度时,RAW264.7 细胞中M1 型巨噬细胞产物IL-1 、iNOS和IL-6 基因表达量最高;而IL-4 以及LPS 联合免疫复合物的刺激作用有显著的剂量依赖性,都在浓度最高时RAW264.7 细胞中Arg1(M2a)和IL-10(M2b)基因表达量最高。LPS 刺激后,A33-3 细胞中IL-1 和iNOS 表达水平明显高于C1-6 细胞,IL-6 则相反;IL-4 及LPS 联合免疫复合物刺激后,A33-3 细胞中Arg1 和IL-10 的表达水平明显低于C1-6 细胞。结论:Aire 可能促进巨噬细胞向M1 极化,同时抑制其向M2a 和M2b 极化。     

巨噬细胞表型极化及其对生物材料植入的影响

巨噬细胞是生物材料植入后诱发的炎症反应及组织修复的主要免疫细胞。近年来探讨生物材料对巨噬细胞表型极化的影响已成为开发新型生物材料的重要评价指标。因此,文章从巨噬细胞表型极化及其与组织再生修复的关系和新型生物材料对于巨噬细胞的影响等几个方面的最新进展进行综述,希望为生物材料在组织工程中开发应用提供参考。     

Effects of a glyconutrient on macrophage functions

Previous studies have shown that mannosylated bovine serum albumin (mBSA) enhances the respiratory burst (RB), phagocytosis, and killing of Candida albicans and Escherichia coli by resident murine peritoneal macrophages (Mphi). Upregulation of the above Mphi functions was associated with the binding of mBSA to the macrophage mannose receptor. The present study was done to determine if certain glyconutrients could stimulate Mphi functions in a similar manner. Resident peritoneal murine Mphi collected from C57BL/6 mice were exposed to the glyconutrients for 10 and 60 min. The RB was measured using chemiluminescence. Both phagocytosis and killing were measured after incubation with each of the following microorganisms: Candida albicans, Escherichia coli and Staphylococcus aureus. The percent phagocytosis and killing were determined using fluorescence microscopy. Results indicated that certain glyconutrients, caused a dose and time dependent effect on Mphi-induced killing of all three microorganisms.     

Effects of tumor-enhancing IgG2 on macrophage function

Macrophages (M phi) play a significant role in allograft rejection. We investigated whether tumor-enhancing (te) IgG(2) acting as a cytophilic opsonin affects allograft destruction. Our results demonstrate that immune Tennessee Swiss (TS) (H-2(s)) mouse M phi destroyed greater numbers of target C3H(f)/He (H-2(k)) tumor cells than did nonimmune M phi. The percentage of (51)Cr release from labeled tumor cells induced by immune M phi was 39.10 + 3.24% compared to nonimmune M phi 28.0 + 3.87%, while te IgG suppressed cytotoxicity toward C3H(f)/He tumor cells of normal TS M phi as manifested by less isotope release (19.60 + 3.13%) than that produced by normal TS M phi with non-enhancing IgG(2) (39.90 + 5.8%). Rather than facilitating survival of allogeneic fibrosarcoma cells, te IgG(2) alloantibody potentiated their destruction by immune TS M phi (isotope release of 52.90 + 3.46%) compared with that produced by immune M phi alone (39.10 + 3.24%). Cytophilic te IgG(2) on TS M phi was demonstrated with either C3H(f)/He red cells or tumor cells. Electron micrographs of M phi revealed tumor cell ingestion and attachment of ferritin-labeled IgG(2) alloantibody on M phi and target tumor cells. In contrast to protection, te IgG(2) alloantibody facilitates macrophage-mediated allograft destruction.     

血源性单核巨噬细胞对小鼠脊髓损伤局部巨噬细胞分化的影响

目的:探讨血源性单核巨噬细胞对小鼠脊髓损伤(SCI)局部巨噬细胞分化的影响.方法:将6～8周龄C57BL/6J雌鼠随机分为两组:SCI+PBS脂质体组(SCIP组)、SCI+氯磷酸二钠脂质体(Chlodrolip)组(SCIL组).两组小鼠分别注射相同剂量两种脂质体.采用流式细胞术(FCM)检测手术前外周血中单核细胞比...     

ROS对小鼠腹腔巨噬细胞凋亡的影响

目的 探讨ＲＯＳ影响巨噬细胞凋亡的机制。方法 激光扫描共聚集显微术,流式细胞术和荧光标记技术等,结果（１）凋亡巨噬细胞内ＤＡＤＰＨ氧化酶活性急剧降低使得胞内ＲＯＳ水平快速上降;（２）ＲＯＳ清除剂促进地塞米松诱导的巨噬细胞凋亡;（３）ＰＫＣ促进巨细胞凋亡和ＲＯＳ急剧减少;ｃＡＭＰ抑制巨噬细胞凋亡和ＲＯＳ急剧减少。结论 （１）ＲＯＳ抑制地塞米松诱导的巨噬细胞凋亡;（２）ＰＫＣ,ｃＡＭＰ等因素通过影响地     

Modelling the macrophage invasion of tumours: Effects on growth and composition

E-mail: owen{at}maths.warwick.ac.uk E-mail: jas{at}maths.warwick.ac.uk Even in the early stages of their development, tumours are notsimply a homogeneous grouping of mutant cells; rather, theydevelop in tandem with normal tissue cells, and also recruitother cell types including lymphatic cells and the endothelialcells required for the development of a blood supply. It hasbeen repeatedly seen that macrophages form a significant proportionof the tumour mass, and that they can have a variety of effectsupon the tumour, leading to a delicate balance between growthpromotion and inhibition. This paper develops a model for theearly, avascular growth of a tumour, concentrating on the inhibitoryeffect of macrophages due to their cytolytic activity. It isshown that such an immune response is not sufficient to preventgrowth, due to it being a second-order process with respectto the density of the tumour cells present However, the presenceof macrophages does have important effects on the tumour composition,and the authors perform a detailed bifurcation analysis of theirmodel to clarify this. An extended model is also consideredwhich incorporates addition of exogenous chemical regulators.In this case, the model admits the possibility of tumour regression,and the therapeutic implications of this are discussed.     

Effects of cholera toxin on macrophage production of co-stimulatory cytokines

Cholera toxin (CT), the enterotoxin of Vibrio cholerae, is a potent mucosal and systemic immunogen and adjuvant. The precise mechanism of the adjuvanticity of CT is poorly understood. Our previous work has showed that CT up-regulates B7.2, but not B7.1 expression on macrophages, and thus increases their co-stimulatory activity. In the current study, the effects of CT on macrophage co-stimulatory cytokine production were investigated. Bone marrow macrophages were generated by culturing bone marrow cells with macrophage colony-stimulating factor. CT treatment increased endotoxin-stimulated macrophage IL-10, IL-6, and IL-1beta production, whereas it decreased IL-12, TNF-alpha and nitric oxide production. Antibody blocking experiments showed that CT inhibition of IL-12 and TNF-alpha production was mediated by increased IL-10 production, in that addition of anti-IL-10 monoclonal antibody abrogated CT inhibition. The decrease in nitric oxide production was in turn secondary to inhibition of TNF-alpha production. Taken together, our study demonstrated that CT has differential effects on various macrophage co-stimulatory cytokines, effects that are likely to contribute to its adjuvanticity.     

Effects of adrenal glands on bone marrow hemopoietic microenvironment

Effects of bilateral adrenalectomy on the hemopoiesis-inducing microenvironment and bone marrow hemopoietic cells were studied. It was shown that adrenal hormones regulate secretory activity of the hemopoiesis-inducing microenvironment, in particular its nonadherent fraction. Adrenalectomy did not change the content of hemopoietic islets, number of erythro- and granulocytopoietic precursors, and blood indexes. The data suggest that structural and functional properties of the hemopoiesis-inducing microenvironment determined by the great variety and high plasticity of organ and intersystem regulatory interactions for a long time compensate the effects of hypocorticism on the requirements for mature blood cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 11, pp. 586–590, November, 1999     

Effects of androgen treatment on expression of macrophage Fcgamma receptors

Macrophage Fcgamma receptors (FcgammaRs) play an important role in the host defense against infection and in the pathophysiology of immune cytopenias. Modulation of macrophage FcgammaR expression is a potential therapeutic approach to immune disorders. Glucocorticoids and progesterones decrease macrophage FcgammaR expression. We assessed the effect of treatment with androgens and antiandrogens on the expression of macrophage FcgammaRs using an experimental guinea pig model. Four androgens (testosterone, dihydrotestosterone, mesterolone, and danazol) and five antiandrogens (flutamide, nilutamide, cyproterone acetate, spironolactone, and finasteride) were studied. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage FcgammaR cell surface expression. All of the androgens impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage FcgammaR expression. Dihydrotestosterone and mesterolone were more effective than testosterone or dihydrotestosterone. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that the androgens decreased the cell surface expression of FcgammaR1,2 more than that of FcgammaR2. Antiandrogens did not significantly alter macrophage FcgammaR expression. Nevertheless, antiandrogens counteracted the effects of androgens on macrophage FcgammaR expression. These data indicate that androgens impair the clearance of IgG-coated cells by decreasing splenic macrophage FcgammaR expression. Thus, androgens other than danazol are candidate drugs for the treatment of immune disorders.     

Effects of antisense oligonucleotides on theexpression of macrophage migration inhibitoryfactor on macrophages

It is well known that the infiltration and prolifera tion of macrophages are the main features in manycases of experimental studies and human glomeru lonephritis, and they also play an important role inthe progressive renal injuries in the development ofglonerulonephritis [ 1 4 ]. Macrophage migrationfactor (MIF) is a proinflammatory cytokine thatwas originally described as a product of activatedlymphocytes that inhibited the random migration ofmacrophages in vitro and promoted the acc…     

Effects of chronic ACTH stimulation on the morphology of the rat adrenal cortex

The effects of chronic ACTH treatment (Depot Synacthen, 100 micrograms/day) on the morphology of the rat adrenal were studied in animals treated for 1 to 18 days. The gross weight of the adrenal increased up to tenfold, but although mitotic figures were seen after 3 days in the glomerulosa region, most of this is attributable to a vast increase in blood content. After 3 days of treatment the sinusoids in the reticularis became extremely dilated, and red blood cells penetrated the endothelial wall to become tightly packed around the cortical cells. This led to the gross distortion of the organization of the cortical tissue and after 7 days the cells in the reticularis region were isolated from each other by the continual infiltration of red blood cells. These changes gradually progressed outward so that other regions of the cortex became similarly affected. Eventually the cord-like arrangement of the fasciculata was disrupted. After 18 days of treatment, most of the cortex was involved and only a very thin layer of cells lying beneath the adrenal capsule was seemingly unaffected. Another major effect of corticotrophin treatment was the gradual loss of cellular differentiation, particularly of glomerulosa cells. Although the glomerulosa appeared normal after 1 day of treatment, cells of the fasciculata abut directly on the connective tissue capsule following 3 days of ACTH administration. Eventually glomerulosa cells disappeared almost completely, although there was no sign of cellular necrosis. It is likely that glomerulosa cells are transformed into fasciculata-type cells under ACTH treatment. This interpretation is consistent with functional changes that occur at the same time, including the loss of aldosterone synthetic capacity.     

Effects of native and oxidized low-density lipoproteins on macrophage chemiluminescence

Effects of low-density lipoproteins (LDL) obtained from healthy donors and patients with hypercholesterolemia on spontaneous luminol-dependent and zymosan-induced chemiluminescence of rat macrophages were studied. Unlike LDL from healthy donors, native LDL from patients with hypercholesterolemia inhibited spontaneous chemiluminescence of macrophages. Simultaneous incubation with endotheliocytes from the umbilical vein led to the appearance of inhibitory effect of LDL from healthy donors (incubation for 24 h) and potentiated this effect of LDL from patients with hypercholesterolemia (incubation for 6 and 24 h). The inhibitory effect was more pronounced in LDL incubated with umbilical endotheliocytes under ischemic conditions then after aerobic incubations. This corresponded to higher oxidation of LDL confirmed by accumulation of thiobarbituric acid-reactive substances, increased fluorescence, and high electrophoretic mobility in agarose gel. These data suggest that the model system of spontaneous and zymosan-induced chemiluminescence of macrophages can be used for evaluating the degree of oxidation and potential atherogenicity of LDL. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 11, pp. 514–517, November, 1999     

重组卡介苗对小鼠巨噬细胞活性及细胞因子产生的影响

目的 将ｒＢＣＧ－ＩＬ－２应用于动脉实验,观察其对肿瘤生长和免疫功能的影响。方法 采用基因工程技术构建ｒＢＣＧ－ＩＬ－２,用黑色素瘤细胞株Ｂ１６接种于小鼠小腿外侧皮下,再用ｒＢＣＧ－ＩＬ－２局部治疗,２ｗｋ处死小鼠,用ＭＴＴＩ地检测腹腔巨噬细胞活必不学无术手淋巴细胞培养上清中ＩＬ－２,ＩＦＮ－ｒ和ＧＭ－ＣＳＦ的含量。结果 ｒＢＣＧ－ＩＬ－２对肿瘤生长的抑制作用与对照组比较有显著性差异Ｐ〈０．０１。     

Effects of antiviral agents on murine cytomegalovirus-induced macrophage dysfunction.

Infection of murine peritoneal macrophages with murine cytomegalovirus (MCMV) led to disruption of phagocytosis. This alteration of cellular behavior appeared to be an early event in viral replication appearing 24 to 36 h before virus production and 84 to 108 h before cell death. The effects of a variety of antiviral agents on both MCMV replication and MCMV-induced depression of phagocytosis were evaluated in vitro. Although all compounds thought to act by preventing viral DNA replication inhibited MCMV replication in macrophages, none prevented expression of virus-induced alteration of phagocytosis. Cycloheximide at 1 microM blocked viral replication and viral antigen expression and prevented depression of phagocytic activity.