Tumor-Associated Inflammatory Cells in Thyroid Carcinomas

The complex interactions between immune cells and tumor cells in cancer play a major role in tumor development and subsequent patient outcomes. Different types of tumor-associated inflammatory cells (TAICs), such as dendritic cells, macrophages, lymphocytes, and mast cells, have been recognized for many years in several tumors; however, the role of TAICs in cancer is still not completely understood. This review article focuses on the major types of TAICs, including their general role in cancer and, more specifically, their role and distribution in thyrocyte-derived carcinomas.     

IL-15 and GM-CSF stimulated macrophages enhances phagocytic activity in ENU induced leukemic mice

Murine splenic macrophage plays a decisive role in host immunity through phagocytosis against pathogens. It was reported that, macrophages also involves in phagocytosis of some tumour cells upon its activation initiated by certain cytokines produced by other immune cell or by indigenously treated. In this study, we have investigated the killing of leukemic blast cells by macrophages upon stimulated with IL-15 and GM-CSF alone or in combination in ENU challenged leukemic murine model. Along with, the release of TNF-α, IL-12 and IFN-γ by macrophages were assayed by ELISA. NO production by macrophages was also investigated. The molecular expressions like GM-CSF and TLRs were investigated for better understand of macrophage-leukemic cell interaction. Result shows that in disease condition macrophages have poor phagocytic activities which may be due to less release of TNF-α, IL-12 and IFN-γ by macrophages. This impaired phagocytic activity in leukemic mice was increase upon stimulation with IL-15 and GM-CSF.     

Effect of candesartan on the expression of sclera-choroidal intercellular adhesion molecule-1 in hypercholesterolemic models

OBJECTIVE:

To evaluate the effect of blocking the angiotensin II AT-1 receptor by the systemic administration of candesartan on the expression of intercellular adhesion molecule-1 in the sclera and choroid of hypercholesterolemic rabbits.

METHODS:

New Zealand rabbits were divided into 3 groups, as follows: GI, which was fed a rabbit standard diet; GII, which was fed a hypercholesterolemic diet; and GIII, which received hypercholesterolemic diet plus candesartan. Samples of the rabbits'' sclera and choroid were then studied by hematoxylin-eosin staining and histomorphometric and immunohistochemical analyses for intercellular adhesion molecule-1 expression.

RESULTS:

Histological analysis of hematoxylin- and eosin-stained sclera and choroid revealed that macrophages were rarely present in GI, and GII had significantly increased macrophage numbers compared to GIII. Moreover, in GII, the sclera and choroid morphometry showed a significant increase in thickness in comparison to GI and GIII. GIII presented a significant increase in thickness in relation to GI. Sclera and choroid immunohistochemical analysis for intercellular adhesion molecule-1 expression revealed a significant increase in immunoreactivity in GII in relation to GI and GIII. GIII showed a significant increase in immunoreactivity in relation to GI.

CONCLUSION:

Candesartan reduced the expression of intercellular adhesion molecule-1 and consequently macrophage accumulation in the sclera and choroid of hypercholesterolemic rabbits.     

Targeted IL‐4 therapy synergizes with dexamethasone to induce a state of tolerance by promoting Treg cells and macrophages in mice with arthritis

F8‐IL‐4 is a recently developed immunocytokine that delivers IL‐4 to sites of inflammation by targeting the neovasculature. We previously reported that F8‐IL‐4, in combination with dexamethasone (DXM), provides a durable therapy in mice with collagen‐induced arthritis (CIA). Therefore, the objective of this study was to identify the mechanism by which IL‐4 and DXM combination therapy provides long‐lasting disease remission. F8‐IL‐4 alone attenuated inflammation in CIA and this was associated with increased T_H2 and decreased T_H17 cell numbers in the joints. Similarly, DXM alone had an antiinflammatory effect associated with lower T_H17 cell numbers. In both cases, these therapeutic benefits were reversed once treatment was stopped. On the other hand, combination therapy with F8‐IL‐4 plus DXM led to a synergistic increase in the percentage of regulatory T (Treg) cells and antiinflammatory macrophages in the arthritic joint and spleen as well as IL‐10 levels in serum and spleen. The net result of this was a more pronounced attenuation of inflammation and, more importantly, protection from arthritis relapse post therapy retraction. In conclusion, F8‐IL‐4 plus DXM is a durable treatment for arthritis that acts by promoting Treg cells in a synergistic manner, and by producing a sustained increase in antiinflammatory macrophages.     

Anti-atherosclerotic action of GW9508 – Free fatty acid receptors activator – In apoE-knockout mice

BackgroundIn the past two decades, enhanced understanding of the biology of G-protein-coupled receptors (GPRs) has led to the identification of several such receptors as novel targets for free fatty acids (FFAs). Two GPRs, FFAR1 and FFAR4, have received special attention in the context of chronic inflammatory diseases, thanks to their anti-inflammatory activities.MethodsThe present study investigates the influence of prolonged treatment with GW9508 – agonist of FFAR1 and FFAR4 – on the development of atherosclerosis plaque in apoE-knockout mice, using morphometric and molecular methods.ResultsGW9508 administration has led to the reduction of atheroscletoric plaque size in an apoE-knockout mice model. Moreover, a FFAR1/FFAR4 agonist reduced the content of macrophages by almost 20%, attributed by immunohistochemical phenotyping to the pro-inflammatory M1-like activation state macrophages.ConclusionsProlonged administration of GW9508 resulted in significant amelioration of atherogenesis, providing evidence that the strategy based on macrophage phenotype switching toward an M2-like activation state via stimulation of FFAR1/FFAR4 receptors holds promise for a new approach to the prevention or treatment of atherosclerosis.     

Role of endothelial progenitors and other bone marrow-derived cells in the development of the tumor vasculature

Increasing evidence suggests the importance of bone marrow-derived cells for blood vessel formation (neovascularization) in tumors, which can occur in two mechanisms: angiogenesis and vasculogenesis. Angiogenesis results from proliferation and sprouting of existing blood vessels close to the tumor, while vasculogenesis is believed to arise from recruitment of circulating cells, largely derived from the bone marrow, and de novo clonal formation of blood vessels from these cells. Although bone marrow-derived cells are crucial for neovascularization, current evidence suggests a promotional role of these cells on the existing blood vessels rather than de novo neovascularization in tumors. This is believed to be due to the highly proangiogenic features of these cells. The bone marrow-derived cells are heterogeneous, consisting of many different cell types including endothelial progenitor cells, myeloid cells, lymphocytes, and mesenchymal cells. These cells are highly orchestrated under the influence of the specific tumor microenvironment, which varies depending on the tumor type, thereby tightly regulating neovascularization in the tumors. In this review, we highlight some of the recent findings on each of these cell types by outlining some of the essential proangiogenic cytokines that these cells secrete to promote tumor angiogenesis and vasculogenesis.     

卡介苗配用腺苷接种提高巨噬细胞抗结核杆菌效能的研究

目的　通过腺苷 (ADO)改善卡介苗 (BCG)初次免疫接种效果 ,提高巨噬细胞抗结核杆菌毒力株效能。方法　将BALB/C小鼠随机分BCG组、ADO组和对照组。对BCG、ADO两组分别一次性皮内注射卡介苗 0 1ml。对ADO组腹腔注射ADO 30mg/(kg·d) ,对BCG组、对照组腹腔注射生理盐水 0 1ml/d ,共 5d。 6周后 ,三组均经血管接种人型结核分枝杆菌标准毒力株 1× 10 6CFU ,BCG组、ADO组于结核杆菌感染后第 10、2 0天和 30天分批取材 ,对照组于第 30天取材。将肺、脾用多聚甲醛固定 ,石蜡包埋 ,HE染色与抗酸染色 ,进行原位细胞凋亡检测。结果　对照组结核杆菌感染后第30天 ,肺组织大部分实变 ,以中性粒细胞浸润为主 ,结核结节多 ,肺实变与肺泡隔重度增宽处弥漫分布大量菌体 ;BCG组于感染后第 10～ 30天肺泡隔增宽 ,逐渐加重至肺大部分实变 ,间质内以淋巴细胞浸润为主 ,结核结节较少 ,肺内大量菌体 ;而ADO组肺实变和肺泡隔重度增宽的面积较小 ,间质内以单核细胞浸润为主 ,结核结节很少 ,肺内菌体明显减少。结论　ADO促进BCG诱导的免疫记忆性反应中能引起单核 巨噬细胞的数量增多和杀菌能力的增强     

Is there a role of taurine bromamine in inflammation? Interactive effects with nitrite and hydrogen peroxide

Objective and Design: The myeloperoxidase system of neutrophils generates chlorinating and brominating oxidants in vivo. The major haloamines of the system are taurine chloramine (TauCl) and taurine bromamine (TauBr). It has been demonstrated in vitro that TauCl exerts both antiinflammatory and anti-bacterial properties. Much less is known about TauBr. The present study was conducted to compare bactericidal and immunoregulatory capacity of TauBr with that of the major chlorinating oxidants: HOCl and TauCl. Moreover, the effect of nitrites and H₂O₂ on TauBr activity was investigated.Materials: TauBr was prepared by reaction of HOBr with taurine. The reaction was monitored by UV absorption spectra.Methods: Bactericidal activity of TauBr, TauCl and HOCl was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the anti-inflammatory activity the compounds were incubated with LPS and IFN- stimulated murine peritoneal macrophages. The production of following mediators was measured: nitrites by Griess reaction; TNF-, IL-6, IL-10, IL-12p40 using capture ELISA. In some experiments the compounds were incubated with either nitrites or H₂O₂.Results: In our experimental set-up TauBr and HOCl exerted strong bactericidal effects on E. coli (MBC = 110 M and 8 M, respectively), while TauCl (< 1000 M) did not kill test bacteria. However, both, TauBr and TauCl, at noncytotoxic concentrations (< 300 M) inhibited the cytokine and nitric oxide production by macrophages. H₂O₂ completely abolished the biological activities of TauBr but not those of TauCl. Nitrites did not affect any activity of TauBr or TauCl while they diminished the HOCl^– mediated bacterial killing.Conclusion: TauBr, despite very low concentration of Br^– in body fluids, may support TauCl and HOCl in the regulation of inflammatory response and in killing of bacteria by neutrophils. However, TauBr activity in vivo will depend on the presence of H₂O₂ and possible other mediators of inflammation which can compete with target molecules for TauBr.Received 16 August 2004; returned for revision 16 September 2004; accepted by A. Falus 13 October 2004     

子宫内膜异位症相关巨噬细胞的研究进展

子宫内膜异位症(EMs)是妇科常见病,表现为血管化的子宫内膜组织在子宫腔以外的部位出现和生长,其发病机制尚未阐明。巨噬细胞是腹腔液中数量最多的白细胞,近年研究表明,巨噬细胞在EMs的发生、发展过程中发挥关键作用。巨噬细胞被招募到EMs微环境中并浸润于EMs组织中,发生选择性活化。活化的巨噬细胞分泌多种细胞因子促进黏附、生长、侵袭,参与信号传递。巨噬细胞吞噬能力受损、凋亡增加,造成了相对免疫耐受的微环境,有助于EMs细胞的存活。巨噬细胞通过分泌血管内皮生长因子(VEGF)和表达Tie-2促进血管新生,在EMs病灶的生长过程中不可或缺。巨噬细胞的许多促EMs发生、发展的作用可能与其在局部发生的选择性活化状态有关。综述巨噬细胞在EMs发生、发展中的作用与功能,此领域的深入研究有助于解释EMs的病因并发展新的免疫学诊疗方法。