M-1/M-2 Macrophages
M-1/M-2巨噬细胞
基本信息
- 批准号:6474178
- 负责人:
- 金额:$ 11.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-08-01 至 2004-07-31
- 项目状态:已结题
- 来源:
- 关键词:B lymphocyte SCID mouse T lymphocyte aminoacid metabolism antineoplastics arginine athymic mouse cell proliferation cytotoxic T lymphocyte enzyme linked immunosorbent assay free radical oxygen helper T lymphocyte immune tolerance /unresponsiveness immunoregulation inflammation interferon alpha interferon beta interferon gamma interleukin 12 interleukin 8 leukocyte activation /transformation macrophage natural killer cells nitric oxide ornithine phenotype
项目摘要
Description (provided by applicant): The goal of this investigation is to more
clearly defme M- 1 and M-2 macrophages and how they influence immune responses.
The concept of M-1 and M-2 fomented from observations in this laboratory that
with the same stimuli, macrophages from certain mice (C57BL/6, B1OD2)
preferentially metabolize argimne to NO while other mice (Balb/c, DBAI2)
increase ornithine production. NO inhibits cell replication while omithine (via
polyamines) promotes cell replication. Therefore, M-1/M-2 does not simply
represent activated or unactivated macrophages, but macrophages that have
upregulated qualitatively different metabolic programs. M-1/M-2 propensities
are also observed in C57BL/6 and Balb/c SCID mice and are thus independent of T
or B lymphocytes. Indeed, other evidence indicates that M-1/M-2 macrophages can
shepherd T lymphocytes into Thi or Th2 responses, respectively. Macrophages are
a major precursor of dendritic cells, which have been reported to influence the
Thl/Th2 balance. Therefore, our results suggest that macrophages play much a
more important role in orchestrating immune responses than is currently
appreciated. The Main Hypothesis is that M-1 is associated with destructive
products and Thl responses, while M-2 is associated with the constructive
products involved in healing/regeneration and with Th2 responses. It is also
hypothesized that overexpression of the M-l phenotype (e.g. NO) can inhibit
specific immune responses. To test these hypotheses Specific Aim 1 will more
clearly define products and properties of M-1/M-2 macrophages including a)
arginine metabolites (NO/ornithine); b) oxygen radicals (O2-, ONOO-, H2O2); and
c) cytokines/growth factors (e.g. IL- 12, IFN-g, IL-8, IFN a/b, macrophage
stimulating protein). Specific Aim I will also determine if M-1/M-2 macrophage
phenotypes are expressed at the single cell level using double color ELISPOT.
Specific Aim 2 will determine how M-l/M-2 macrophage responses influence
non-specific or specific immune responses in vivo. Specific Aim 2a will
determine how M-1/M-2 macrophage responses influence non-specific inflammation
associated with injury/danger. Specific Aim 2b will compare innate immunity in
M-l/M-2-dominant mice. Specific Aim 2c will determine how M- 1 /M-2 macrophages
influence tumor specific or allo specific immune responses. M1 (C578L/6) and
M-2 (Balb/c) SCID mice will be used extensively as test subjects and as sources
of macrophages for adoptive transfer to directly determine effects due to
M-1/M-2 macrophages. Together, this investigation will result in a major
increase in our understanding of M-1/M-2 macrophages and how they influence
immune responses.
描述(由申请人提供):这项调查的目的是向更多
显然,DEFME M-1和M-2巨噬细胞以及它们如何影响免疫反应。
M-1和M-2的概念从该实验室的观察中引起了人们的注意
使用相同的刺激,来自某些小鼠的巨噬细胞(C57BL/6,B1OD2)
优先将Argimne代谢为没有其他小鼠(BALB/C,DBAI2)
增加鸟氨酸的产生。无抑制细胞复制时(通过
多胺)促进细胞复制。因此,M-1/M-2不简单
代表激活或未激活的巨噬细胞,但具有
上调定性不同的代谢程序。 M-1/M-2倾向
在C57BL/6和BALB/C SCID小鼠中也观察到,因此独立于T
或B淋巴细胞。实际上,其他证据表明M-1/M-2巨噬细胞可以
牧羊人T淋巴细胞分别为Thi或Th2反应。巨噬细胞是
树突状细胞的主要前体,据报道会影响
THL/TH2平衡。因此,我们的结果表明巨噬细胞发挥了很大的作用
在编排免疫反应中比目前更重要的作用
感谢。主要假设是M-1与破坏性有关
产品和THL响应,而M-2与建设性相关
涉及愈合/再生和TH2反应的产品。也是
假设M-L表型(例如NO)的过表达可以抑制
特定的免疫反应。为了检验这些假设,具体目标1将更多
清楚地定义了M-1/M-2巨噬细胞的产品和特性,包括a)
精氨酸代谢产物(无/鸟氨酸); b)氧自由基(O2-,Onoo-,H2O2);和
C)细胞因子/生长因子(例如IL-12,IFN-G,IL-8,IFN A/B,巨噬细胞
刺激蛋白)。具体目的我还将确定是否M-1/M-2巨噬细胞
使用双色ELISPOT在单细胞水平上表达表型。
特定的目标2将确定M-L/M-2巨噬细胞反应如何影响
体内非特异性或特异性免疫反应。特定的目标2a将
确定M-1/M-2巨噬细胞反应如何影响非特异性炎症
与伤害/危险有关。特定的目标2b将比较先天免疫
M-L/M-2主导小鼠。特定的AIM 2C将确定M-1 /M-2巨噬细胞如何
影响肿瘤特异性或特异性免疫反应。 M1(C578L/6)和
M-2(BALB/C)SCID小鼠将广泛用作测试对象和来源
巨噬细胞用于收养转移以直接确定由于
M-1/M-2巨噬细胞。一起,这项调查将导致一个重大
提高我们对M-1/M-2巨噬细胞的理解及其如何影响
免疫反应。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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CHARLES D MILLS其他文献
CHARLES D MILLS的其他文献
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{{ truncateString('CHARLES D MILLS', 18)}}的其他基金
INJURY AND LEUKOCYTE STIMULATION OF TUMOR GROWTH
损伤和白细胞刺激肿瘤生长
- 批准号:
6296734 - 财政年份:1998
- 资助金额:
$ 11.14万 - 项目类别:
INJURY AND LEUKOCYTE STIMULATION OF TUMOR GROWTH
损伤和白细胞刺激肿瘤生长
- 批准号:
6107684 - 财政年份:1998
- 资助金额:
$ 11.14万 - 项目类别:
INJURY AND LEUKOCYTE STIMULATION OF TUMOR GROWTH
损伤和白细胞刺激肿瘤生长
- 批准号:
6217834 - 财政年份:1998
- 资助金额:
$ 11.14万 - 项目类别:
INJURY AND LEUKOCYTE STIMULATION OF TUMOR GROWTH
损伤和白细胞刺激肿瘤生长
- 批准号:
6296730 - 财政年份:1998
- 资助金额:
$ 11.14万 - 项目类别:
INJURY AND LEUKOCYTE STIMULATION OF TUMOR GROWTH
损伤和白细胞刺激肿瘤生长
- 批准号:
6296726 - 财政年份:1998
- 资助金额:
$ 11.14万 - 项目类别:
NITRIC OXIDE AND INSULIN IN ISLET TRANSPLANTATION
胰岛移植中的一氧化氮和胰岛素
- 批准号:
6177536 - 财政年份:1997
- 资助金额:
$ 11.14万 - 项目类别:
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