Induction of CCR2-dependent macrophage accumulation by oxidized phospholipids in the air-pouch model of inflammation.
Induction of CCR2-dependent macrophage accumulation by oxidized phospholipids in the air-pouch model of inflammation.
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DOI：
10.1002/art.24448
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发表时间：
2009-05
影响因子：
--
通讯作者：
Leitinger, Norbert
中科院分区：
文献类型：
--
作者：
Kadl, Alexandra;Galkina, Elena;Leitinger, Norbert
巨噬细胞在类风湿性滑膜炎和动脉粥样硬化的发病机制中起关键作用。为了确定致动脉粥样硬化的氧化磷脂是否可能导致滑膜炎症和随后的单核细胞/巨噬细胞募集，我们使用小鼠气囊模型在体内研究了氧化1-棕榈酰-2-花生四烯酸-sn-3-甘油-磷酸胆碱（OxPAPC）对复制滑膜中趋化因子表达和白细胞募集的影响。通过2次注射无菌空气使气囊升高，并通过将脂多糖（LPS）或OxPAPC注射到气囊腔中诱导炎症。通过使用逆转录-聚合酶链反应或免疫组织化学分析的炎症基因表达的分析来评估炎症，并且在用Giemsa染色或在酶消化之后通过荧光激活的细胞分选仪分析来量化灌洗液和囊壁中的白细胞。应用OxPAPC导致单核细胞/巨噬细胞选择性募集到气囊壁中，但不在管腔中。相反，LPS诱导单核细胞和中性粒细胞积聚在囊腔以及壁中。LPS诱导粘附分子E-选择素、P-选择素、细胞间粘附分子1和血管细胞粘附分子1的表达，而OxPAPC不诱导。OxPAPC可增加巨噬细胞上CCR 2配体单核细胞趋化蛋白1（MCP-1）、MCP-3和MCP-5以及RANTES和生长相关癌基因α（GROα）的表达，同时下调CCR 2的表达。此外，在CCR 2 −/−小鼠中，氧化磷脂诱导的巨噬细胞蓄积被消除。这些数据表明，氧化磷脂触发一种类型的炎症反应，导致体内选择性巨噬细胞积累，慢性炎症性风湿性疾病的发病机制相关的过程。
Macrophages are key players in the pathogenesis of rheumatoid synovitis as well as in atherosclerosis. To determine whether atherogenic oxidized phospholipids potentially contribute to synovial inflammation and subsequent monocyte/macrophage recruitment, we examined the effects of oxidized 1-palmitoyl-2-arachidonoyl-sn-3-glycero-phosphorylcholine (OxPAPC) on chemokine expression and leukocyte recruitment in a facsimile synovium in vivo using the murine air-pouch model. Air pouches were raised by 2 injections of sterile air, and inflammation was induced by injecting either lipopolysaccharide (LPS) or OxPAPC into the pouch lumen. Inflammation was assessed by analysis of inflammatory gene expression using reverse transcription–polymerase chain reaction or immunohistochemical analysis, and leukocytes were quantified in the lavage fluid and in the pouch wall after staining with Giemsa or after enzymatic digestion followed by fluorescence-activated cell sorter analysis. Application of OxPAPC resulted in selective recruitment of monocyte/macrophages into the air-pouch wall, but not in the lumen. In contrast, LPS induced both monocyte and neutrophil accumulation in the pouch lumen as well as in the wall. LPS, but not OxPAPC, induced the expression of adhesion molecules E-selectin, P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. OxPAPC increased the expression of the CCR2 ligands monocyte chemotactic protein 1 (MCP-1), MCP-3, and MCP-5, as well as RANTES and growth-related oncogene α (GROα), while it down-regulated the expression of CCR2 on macrophages. Moreover, oxidized phospholipid–induced macrophage accumulation was abrogated in CCR2−/− mice. These data demonstrate that oxidized phospholipids trigger a type of inflammatory response that leads to selective macrophage accumulation in vivo, a process relevant for the pathogenesis of chronic inflammatory rheumatic diseases.
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影响因子：
4
作者：
Kadl, A;Huber, J;Leitinger, N
通讯作者：
Leitinger, N
影响因子：
4.8
作者：
Krönke, G;Bochkov, VN;Leitinger, N
通讯作者：
Leitinger, N
DOI：
10.1161/01.atv.6.3.254
发表时间：
1986-05-01
期刊：
ARTERIOSCLEROSIS
影响因子：
--
作者：
BERLINER, JA;TERRITO, M;FOGELMAN, AM
通讯作者：
FOGELMAN, AM
在动脉粥样硬化之前和开发过程中淋巴细胞募集到主动脉壁是部分依赖性L-选择蛋白。
DOI：
10.1084/jem.20052205
发表时间：
2006-05-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Bochkov, VN;Kadl, A;Leitinger, N
通讯作者：
Leitinger, N