O—LDL与动脉粥样硬化研究的新进展

氧化修饰低密度脂蛋白(O—LDL)在动脉粥样硬化发生发展中的作用,日益受到人们的重视。特别是作为唯一能有效地缓解纯合子型家族性胆固醇血症患者的皮肤和肌腱黄色瘤及阻止纯合子型Watanabe遗传性高脂血症家兔动脉粥样硬化发展的降胆固醇药物Probucol,现在知道是一种抗氧化剂,它的治疗作用是通过阻止低密度脂蛋白(LDL)氧化修饰,而不是它的降胆固醇效应。已有大量的研究说明氧化修饰的低密度脂蛋白在动脉粥样硬化发生发展中具有重要作用。近年来研究在不断深入,特别是发现最小修饰LDL对基因的调控。它在体外能诱导内皮细胞(EC)JE基因mRNA表达和使单核细胞化学趋向性蛋白—1(MCP—1)含量增加,从基因水平说明动脉粥样硬化病变早期单核细胞粘着于内皮细胞与机体受到脂质过氧化损伤有关。MM—LDL静脉注射能使血液M—CSF含量升高,组织JE基因mRNA表达增加,富含巨噬细胞的主动脉病变区含有O—LDL和与其有关的特有的活性蛋白和mRNA,以及冠心病患者冠状动脉扩张反应减弱与O—LDL对内皮细胞、内皮依赖性扩张因子和平滑肌细胞的作用有关,从不同水平的实验进一步说明O—LDL在动脉粥样硬化发生发展中的作用。     

氧化修饰低密度脂蛋白对巨噬细胞的脂质过氧化损伤在泡沫细胞形成中的作用

氧化修饰低密度脂蛋白(Ox—LDL)在动脉粥样硬化发生发展中的作用越来越引起人们的重视。本文通过比较Ox—LDL和脂质过氧化降解产物丙二醛(MDA)修饰的低密度脂蛋白(MDA—LDL)在致泡沫细胞形成方面的差异,探讨了脂质过氧化对巨噬细胞的损伤在泡沫细胞形成中的作用。结果显示:Ox—LDL和MDA—LDL都可被巨噬细胞清道夫受体所识别,引起大量吞噬,造成细胞内胆固醇的聚集,但由MDA—LDL造成的细胞内胆固醇酯聚集可被高密度脂蛋白(HDL_3)所清除,而Ox—LDL造成的胆固醇酯聚集则不能。进一步的研究表明Ox—LDL和MDA—LDL对巨噬细胞HDL_3结合量及细胞内脂质过氧化物(LPO)含量的影响不同。虽然MDA—LDL和Ox—LDL处理巨噬细胞,都可使其HDL_3结合量有不同程度的下降,细胞内LPO含量有不同程度的升高,但当处理因素消除后,细胞继续培养时,由MDA—LDL处理的细胞其降低的HDL_3结合量又有一定的恢复,细胞LPO含量不再上升;而由Ox—LDL处理的细胞,其HDL_3结合量则继续下降,细胞LPO含量则继续升高。由Ox—LDL导致的巨噬细胞HDL_3结合量下降与细胞LPO含量升高之间呈负相关(r=-0.81,P<0.01)。用叔丁基脂氢过氧化物(tbooh)(1×10~(?)mol/L)对巨噬细胞损伤24小时,然后用两种修饰的LDL处理,则两种修饰LDL造成的胆固醇酯聚集都不能被HDL_3清除。本文结果提示Ox—LDL对巨噬细胞的脂质过氧化损伤可能在巨噬细胞向泡沫细胞转变过程中起着重要作用。     

氧化修饰低密度脂蛋白对巨噬细胞的脂质过氧化损伤在泡沫细胞形成中的作用

氧化修饰低密度脂蛋白(Ox—LDL)在动脉粥样硬化发生发展中的作用越来越引起人们的重视。本文通过比较Ox—LDL和脂质过氧化降解产物丙二醛(MDA)修饰的低密度脂蛋白(MDA—LDL)在致泡沫细胞形成方面的差异,探讨了脂质过氧化对巨噬细胞的损伤在泡沫细胞形成中的作用。结果显示:Ox—LDL和MDA—LDL都可被巨噬细胞清道夫受体所识别,引起大量吞噬,造成细胞内胆固醇的聚集,但由MDA—LDL造成的细胞内胆固醇酯聚集可被高密度脂蛋白(HDL₃)所清除,而Ox—LDL造成的胆固醇酯聚集则不能。进一步的研究表明Ox—LDL和MDA—LDL对巨噬细胞HDL₃结合量及细胞内脂质过氧化物(LPO)含量的影响不同。虽然MDA—LDL和Ox—LDL处理巨噬细胞,都可使其HDL₃结合量有不同程度的下降,细胞内LPO含量有不同程度的升高,但当处理因素消除后,细胞继续培养时,由MDA—LDL处理的细胞其降低的HDL₃结合量又有一定的恢复,细胞LPO含量不再上升;而由Ox—LDL处理的细胞,其HDL₃结合量则继续下降,细胞LPO含量则继续升高。由Ox—LDL导致的巨噬细胞HDL₃结合量下降与细胞LPO含量升高之间呈负相关(r=-0.81,p<0.01)。用叔丁基脂氢过氧化物(tbooh)(1×10~(?)mol/L)对巨噬细胞损伤24小时,然后用两种修饰的LDL处理,则两种修饰LDL造成的胆固醇酯聚集都不能被HDL₃清除。本文结果提示Ox—LDL对巨噬细胞的脂质过氧化损伤可能在巨噬细胞向泡沫细胞转变过程中起着重要作用。     

尼卡地平对低密度脂蛋白氧化及巨噬细胞泡沫化过程中脂质代谢的影响

目的 :观察钙通道阻滞剂尼卡地平对低密度脂蛋白 (LDL)体外氧化以及对小鼠腹腔巨噬细胞泡沫化过程中细胞内脂质代谢两个环节的影响 ,探讨钙通道阻滞剂抗动脉粥样硬化 (AS)的作用机制。方法 :采用Cu2 + 氧化LDL ,动态监测LDL氧化修饰过程中 2 34nm处紫外吸光度及丙二醛 (MDA)含量的变化 ,观察不同浓度尼卡地平 (10 μmol/L、10 0 μmol/L)对体外LDL氧化修饰的抑制作用。收集和培养纯系 6 15小鼠腹腔巨噬细胞 ,将其分成 4组 :①对照组 ,②氧化修饰LDL(ox LDL)组 ,③ox LDL加 10 μmol/L尼卡地平组 ,④ox LDL加 10 0μmol/L尼卡地平组 ,培养 4 8h后 ,分别测定细胞内总胆固醇 (TC)、游离胆固醇 (FC)及胆固醇酯 (CE) ,观察不同浓度尼卡地平对小鼠腹腔巨噬细胞泡沫化过程中细胞内脂质代谢的影响。结果 :①尼卡地平可以降低LDL氧化修饰过程中 2 34nm吸光度峰值 ,明显延长迟滞期 ,使氧化曲线右移 ,且存在剂量效应关系。 10 μmol/L及 10 0μmol/L尼卡地平分别将迟滞期延长33.96 %和 6 9.6 5 % ,与对照组比较差异均有显著性意义 (均P <0 .0 5 )。同时 ,尼卡地平可以减少MDA的生成量 ,10 0 μmol/L尼卡地平抑制MDA生成量更明显 ,MDA减少 2 1%。②ox LDL组细胞内TC、FC及CE较对照组均显著增高 (均P <0 .0 1) ,巨噬     

造血生长因子的临床应用

近年来,重组DNA技术已能生产5种造血生长因子,包括促红细胞生成素(EPO),粒—巨噬细胞克隆刺激因子(GM—CSF),粒细胞克隆刺激因子(G—CSF),巨噬细胞克隆刺激因子(M—CSF)及白细胞介素Ⅲ(IL—3)。其中EPO、     

粒细胞——巨噬细胞集落刺激因子的研究现状及临床应用

集落刺激因子(Colony Stimulating Factors)是一组控制粒细胞、单核一巨噬细胞和某些有关的造血细胞增殖和分化的糖蛋白,根据不同的分化阶段和造血祖细胞,分为粒细胞一巨噬细胞集落刺激因子(GM—CSF)、粒细胞集落刺激因子(G—CSF)、巨噬细胞集落刺激因子(M—CSF)以及多潜能集落刺激因子(Multi—CSF)又称白细胞介素—3(IL—3)。现就近年来GM—CSF研究进展及临床应用综述如下。     

氧化低密度脂蛋白引起动脉粥样硬化机制

高胆固醇血症特别血中LDL升高,众所周知是AS的主要危险因子,血中LDL升高,作为引起AS主要机制之—与OX-LDL增多有关。本文主要叙述OX-IDL在AS中的作用。1 AS初期病变 AS初期内皮细胞下有局灶性成堆的巨噬细胞浸润,这些细胞内蓄积大量胆固醇酯,称为泡沫细胞,这些泡沫细胞来     

VLDL和ox-LDL对单核巨噬细胞的作用及机制探讨

目的:探讨极低密度脂蛋白(VLDL)、氧化修饰的低密度脂蛋白(ox-LDL)对单核巨噬细胞的作用及机制。方法:分析VLDL、ox—LDL对单核巨噬细胞清道夫受体A(SRA)、VLDL受体(VLDLR)基因转录、细胞因子肿瘤坏死因子(TNF—α)、基质金属蛋白酶(MMP-9)蛋白质表达,以及细胞生长状态的影响。结果:①VLDL增加ox-LDL介导的巨噬细胞SRA mRNA及蛋白质表达,ox—LDL则能增加VLDL介导的巨噬细胞VLDLR基因转录;②VLDL与ox—LDL协同作用显著减少巨噬细胞抗脂质摄取载脂蛋白E分泌;③两种脂蛋白能诱导巨噬细胞TNF-α及MMP-9释放,并能抑制巨噬细胞凋亡,促进增殖。结论:VLDL、ox-LDL对单核巨噬细胞增生、细胞因子释放及脂蛋白受体表达均有协同作用,可能体内的情况多为两种脂蛋白的协同作用。     

粒-巨噬细胞集落刺激因子在肺表面活性物质稳态调节中的作用

粒 巨噬细胞集落刺激因子 (GM CSF)是一种细胞生长因子 ,常用于化疗及骨髓移植后刺激造血恢复。近年通过转基因动物的研究发现 ,GM CSF或其受体基因敲除鼠并未出现造血系统紊乱 ,唯一的病理改变是肺内表面活性物质磷脂和蛋白的蓄积。该研究提示GM CSF在造血系统稳态调节中作用甚微 ,而在肺表面活性物质的代谢平衡中却起着至关重要的作用。这为临床上肺泡蛋白沉积症的诊断及治疗提供了有益的启示     

M1和M2型巨噬细胞经ox LDL刺激后细胞内脂质含量及分泌TNF α、IL 10的浓度差别与意义

目的：探讨 M1和 M2型巨噬细胞经氧化型低密度脂蛋白（ox LDL）刺激后细胞内脂质含量及分泌的细胞因子白细胞介素10（IL 10）、肿瘤坏死因子（TNF α）的浓度差别及意义。方法提取 C57BL/6小鼠的骨髓单核细胞,用巨噬细胞集落刺激因子（M CSF）诱导其向巨噬细胞分化,并辅以干扰素γ（IFN γ）和白细胞介素4（IL 4）刺激巨噬细胞向M1和M2型分化,行RT PCR检测极化后 M1型巨噬细胞的标志物一氧化氮合成酶（iNOS）及 M2型巨噬细胞的标志物精氨酸酶（Arg1）的表达。M1及 M2型巨噬细胞诱导分化成功后在40 mg/L ox LDL中培育48 h后行油红O染色观察细胞内脂质含量;行ELISA检测上清液中IL 10和TNF α的浓度。结果 RT PCR结果显示Arg1的表达在IFN γ刺激组低于IL 4刺激组,而iNOS的表达在IFN γ刺激组高于IL 4刺激组,表明 IFN γ刺激后巨噬细胞分化为 M1型而 IL 4刺激后分化为 M2型;油红 O染色示 M1和 M2型巨噬细胞内的脂质含量均高于对照组,M1型巨噬细胞内脂质含量高于 M2型巨噬细胞。ELISA检测示 M1和M2型巨噬细胞上清液中TNF α和IL 10浓度均高于对照组,差异有统计学意义（P〈0.05）;M1型巨噬细胞上清液中 IL 10浓度低于 M2型巨噬细胞,而 TNF α的浓度则高于 M2型巨噬细胞,差异有统计学意义（P〈0.05）。结论 M1型巨噬细胞可能通过分泌 TNF α增强对胆固醇的摄入,加速动脉粥样硬化的发生发展,而 M2型巨噬细胞可能通过分泌 IL 10减少对胆固醇的吞噬,从而发挥抗 AS作用。     

Peritoneal fluid and plasma levels of human macrophage colony-stimulating factor in relation to peritoneal fluid macrophage content

The peritoneal fluid (PF) of women with infertility (especially in the presence of endometriosis) contains increased numbers of leukocytes, 90% to 95% of which are macrophages. The high numbers of peritoneal macrophages presumably result from an influx of blood monocytes into the peritoneum, and/or from local proliferation of peritoneal macrophages. Once in the peritoneal cavity, monocytes differentiate into tissue macrophages. Mononuclear phagocyte proliferation and differentiation are influenced by different cytokines, including macrophage colony-stimulating factor (M-CSF). The purpose of this study was to determine the relationship of M-CSF levels in human PF and plasma to the macrophage content, and to the patient diagnoses. Mean concentrations of PF M-CSF were higher than plasma levels (2.44 +/- 0.13 v 0.95 +/- 0.06 ng/mL, respectively). The mean concentrations of plasma M-CSF did not differ in samples from women of different diagnostic groups (normal, peritoneal adhesions, endometriosis, inactive pelvic inflammatory disease, uterine fibroids, and idiopathic infertility), but the PF concentration was slightly higher in normal women. The absolute (total) amount of PF M-CSF in normal women was lower than in those of the other diagnostic groups. The total amount of PF M-CSF in all women correlated closely with the total number of peritoneal macrophages. The tubal patency status (open versus closed) did not influence the plasma and PF concentrations of M-CSF, nor the PF absolute amount of M-CSF. The PF M-CSF may have come from peritoneal macrophages, fibroblasts, mesothelial cells, or endothelial cells. PF M-CSF may play important roles in the proliferation and/or the differentiation of peritoneal mononuclear phagocytes.     

Macrophages can recognize and kill tumor cells bearing the membrane isoform of macrophage colony-stimulating factor

NBXFO hybridoma cells produced both the membrane and secreted isoforms of macrophage colony-stimulating factor (M-CSF). Murine bone marrow cells stimulated by the secreted form of M-CSF (sM-CSF) became Mac1+, Mac2+, Mac3+, and F4/80+ macrophages that inhibited the growth of NBXFO cells, but not L1210 or P815 tumor cells. In cytotoxicity studies, M- CSF activated macrophages and freshly isolated macrophages killed NBXFO cells in the presence of polymyxin B, eliminating the possibility that contaminating lipopolysaccharide (LPS) was responsible for the delivery of the cytotoxic signal. Retroviral-mediated transfection of T9 glioma cells with the gene for the membrane isoform of M-CSF (mM-CSF), but not for the secreted isoform of M-CSF, transferred the ability of macrophages to kill these transfected T9 cells in a mM-CSF dose- dependent manner. Macrophage-mediated killing of the mM-CSF transfected clone was blocked by using a 100-fold excess of recombinant M-CSF. Catalase, superoxide dismutase, and the nitric oxide inhibitor, N-omega- nitro-arginine methyl ester (NAME), did not effect macrophage cytotoxicity against the mM-CSF transfectant T9 clones. T9 parental cells when cultured in the presence of an equal number of the mM-CSF transfectant cells were not killed, indicating specific target cell cytotoxicity by the macrophages. Electron microscopy showed that macrophages were capable of phagocytosizing mM-CSF bearing T9 tumor cells and NBXFO hybridoma cells; this suggested a possible mechanism of this cytotoxicity. This study indicates that mM-CSF provides the necessary binding and triggering molecules through which macrophages can initiate direct tumor cell cytotoxicity.     

Macrophage colony-stimulating factor reduces tert-butyl hydroperoxide induced oxidative injury to monocytes/macrophages.

The transformation of macrophages into foam cells is an important event in the development of atherosclerosis, and the oxidative injury caused by oxidized low density lipoprotein (Ox-LDL) plays an essential role in that process. It has been proved that macrophage colony-stimulating factor (M-CSF) could prevent the progression of atherosclerosis in Watanabe heritable hypercholesterolemic (WHHL) rabbits. We proposed that the anti-atherogenic effect of M-CSF was partly associated with its protective effect on monocyte-derived macrophages from Ox-LDL induced oxidative injury. In order to prove this, we investigated the effect of M-CSF on the oxidative injury caused by tert-butyl hydroperoxide (tbOOH) to mouse peritoneal macrophages and U937/J774 cell lines. The results showed that M-CSF could protect mouse peritoneal macrophages from oxidative injury (presented by cell morphology and cell survival rate); L929 cell-conditioned medium (L929-CM) had the same effect as M-CSF; and anti-M-CSF monoclonal antibody could mostly block the protective effect of L929-CM on macrophages. L929-CM was proved to be also able to decrease the impact of plasma membrane fluidity in U937 and J774 cells treated with tbOOH. Incubation with tbOOH caused DNA fragmentation in U937 cells. The presence of L929-CM greatly reduced the number of apoptotic U937 cells characterized by DNA fragmentation. From these results, we concluded that M-CSF could protect monocytes/macrophages from oxidative injury. It may be one of the mechanisms which explain the anti-atherogenic effect of exogenous M-CSF in WHHL rabbits.     

Contribution of monocyte chemoattractant protein-1 and c-fms/macrophage colony-stimulating factor receptor to coronary artery disease: analysis of human coronary atherectomy specimens

OBJECTIVES: Primary coronary atherosclerotic lesions(de novo lesions) are a type of inflammatory vascular disease. Restenotic lesions after percutaneous coronary intervention mainly consist of proliferative vascular smooth muscle cells. Recent studies have demonstrated that locally synthesized cytokines, including chemokines, are important in both these coronary lesions. Monocyte chemoattractant protein(MCP)-1 and macrophage colony-stimulating factor(M-CSF) are two of the associated chemokines, but their role in coronary artery disease has not been sufficiently clarified. This study investigated the expression of MCP-1 and c-fms/M-CSF receptor in human coronary tissues. METHODS: Histological and immunohistochemical studies used samples obtained from patients who underwent directional coronary atherectomy(28 de novo lesions and 16 restenotic lesions). The following primary antibodies were used: anti-MCP-1, anti-c-fms, anti-macrophages and anti-alpha-smooth muscle actin. RESULTS: Focal accumulation of macrophage-derived foam cells, thrombus, cholesterol clefts and calcification tended to be more frequent in de novo lesions than in restenotic lesions. On the other hand, restenotic lesions mainly consisted of stellate vascular smooth muscle cells and extracellular matrix. The expression of MCP-1-positive cells almost coincided with the macrophages. In contrast, staining for MCP-1 was little seen in the stellate vascular smooth muscle cells. Expression of c-fms was found in both macrophages and stellate vascular smooth muscle cells. Expression patterns of MCP-1 and c-fms exhibited no difference between the two lesion types. CONCLUSIONS: Both MCP-1 and the M-CSF/c-fms system are involved in the atherogenesis of de novo lesions. However, the M-CSF/c-fms system, rather than MCP-1, is more important in the late stage of restenosis.     

HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and inhibits M-CSF bioactivities

HIV-1 Nef protein is a major determinant of the pathogenicity of the virus. It has been shown that Nef activates Hck, a member of Src family kinase, in monocytes/macrophages and that the interaction is critical for AIDS-like disease progression in a mouse model. However, it was unclear how the molecular interaction in monocytes/macrophages leads to disease progression. Here, we show for the first time that Nef interferes with the macrophage colony-stimulating factor (M-CSF)/M-CSF receptor signal pathway. In this study, we introduced a conditionally active Nef into myeloid leukemia TF-1-fms cells and analyzed their responsiveness to M-CSF. We found that Nef-activated Hck constitutively associated with the M-CSF receptor complex. The formation of the molecular complex should occur under physiologic conditions, that is, on M-CSF stimulation. Because of aberrant molecular association, the tyrosine-phosphorylation/activation of the receptor in response to M-CSF was markedly diminished in Nef-active cells. Consequently, Nef activation caused the inhibition of M-CSF-mediated proliferation of TF-1-fms cells and macrophage differentiation of the cells induced by M-CSF and 12-O-tetradecanoylphorbol 13-acetate. These results indicate that HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and thereby inhibits M-CSF functions in monocytes/macrophages.     

Effect of mouse interferon on growth and differentiation of mouse bone marrow cells stimulated by two different types of colony-stimulating factor

The effects of mouse L-cell interferon (IFN) on growth of mouse bone marrow cells and their differentiation into macrophages and granulocytes were investigated in a liquid suspension culture system with two different types of colony-stimulating factor (CSF). Within 7 days, most bone marrow cells differentiated into macrophages in the presence of macrophage colony-stimulating factor (M-CSF) derived from mouse fibroblast L929 cells, but into both granulocytes (40%) and macrophages (23%) in the presence of a granulocyte-macrophage colony- stimulating factor (GM-CSF) from mouse lung tissue. IFN inhibited growth of bone marrow cells with both M-CSF and GM-CSF, but had 20 times more effect on bone marrow cells stimulated with M-CSF than on those stimulated with GM-CSF. A low concentration of IFN (50 IU/ml) stimulated production of macrophages by GM-CSF in liquid culture medium, whereas it selectively inhibited colony formation of macrophages in semisolid agar culture. IFN caused no detectable block of late stages of differentiation; mature macrophages and granulocytes were produced even when cell proliferation was inhibited by IFN. These results indicate that IFN preferentially affects growth and differentiation of the cell lineage of macrophages among mouse bone marrow cells.     

Macrophage colony-stimulating factor aggravates rather than regenerates emphysematous lungs in mice

BACKGROUND: Lung regeneration is an innovative strategy that may cure pulmonary emphysema. The bone marrow (BM) harbors pulmonary stem cells. Hematopoietic cytokine-driven mobilization of BM cells may thus support lung regeneration. OBJECTIVES: The aim of this study was to determine whether systemic administration of macrophage colony-stimulating factor (M-CSF) leads to the regeneration of lungs in a murine model of elastase-induced emphysema. METHODS: C57BL/6J mice were administered elastase intratracheally. Four weeks later, in the absence or presence of elastase treatment, mice were intraperitoneally given either M-CSF or saline on days 1-5 each week for 3 weeks. Lung tissue was harvested 24 h after the last injection. RESULTS: M-CSF administration without prior elastase did not affect the mean linear intercept, surface area, or surface area/lung volume. In contrast, M-CSF administration following elastase injury caused a greater increase in the mean linear intercept and greater decreases in surface area and surface area/lung volume than saline administration following elastase, indicating that M-CSF aggravated emphysema. This aggravation of emphysema was accompanied by accumulation of pulmonary alveolar macrophages (AMs) expressing metalloproteinase (MMP)-9 and MMP-12. M-CSF stimulated AMs to express MMPs in vitro. CONCLUSIONS: These results suggest that M-CSF administration does not support lung regeneration but rather aggravates the lung destruction associated with elastase injury.     

Macrophage colony-stimulating factor enhances the susceptibility of macrophages to infection by human immunodeficiency virus and reduces the activity of compounds that inhibit virus binding

The effects of macrophage colony-stimulating factor (M-CSF) on CD4 receptor expression, susceptibility to human immunodeficiency virus type 1 (HIV) infection, and anti-HIV activity of dextran sulfate and soluble-CD4 were studied in cultured, human primary macrophages. M-CSF stimulated macrophage cells to express the CD4 receptor, and this resulted in an increase of both the number of CD4+ cells and the density of the receptor on the cell surface. M-CSF also significantly enhanced the susceptibility of macrophage cells to HIV infection. Interestingly, the anti-HIV activity of dextran sulfate and soluble-CD4 (two compounds that interfere with HIV-CD4 binding with different mechanisms) was reduced 100-fold and fivefold, respectively, in M-CSF- treated macrophages. Human blood concentrations of M-CSF are reported to be similar to those used in this work (1,000 U/mL); thus, it is conceivable that also in vivo this cytokine may modify the susceptibility of macrophages to HIV and the ability of dextran sulfate and soluble CD4 to inhibit HIV replication. These results suggest that the in vitro study in M-CSF-treated macrophages of promising drugs inhibitors of HIV-CD4 binding could provide further insights into the potential efficacy of these compounds in patients.     

Signal Transduction in Macrophages: Negative Regulation for Macrophage Colony-Stimulating Factor Receptor Signaling

The receptor for macrophage colony-stimulating factor (M-CSF) is expressed in monocytes/macrophages and their progenitor cells and stimulates both the growth and development of the blood-cell lineage. Although the specific components positively regulating M-CSF receptor signaling have been relatively well defined, it is now clear that important mechanisms to control the signaling cascades also exist. This review discusses the most recent results concerning the negative regulatory molecules for M-CSF receptor signaling. In particular, we focus on negative molecules for both proliferation of monocytes/macrophages and differentiation into mature cells.