Sol Sherry lecture in thrombosis - Molecular events in acute inflammation
Sol Sherry lecture in thrombosis - Molecular events in acute inflammation
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DOI：
10.1161/01.atv.0000016153.47693.b2
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发表时间：
2002-05-01
影响因子：
8.7
通讯作者：
Stafforini, DM
中科院分区：
文献类型：
--
作者：
Prescott, SM;McIntyre, TM;Stafforini, DM
炎症反应的特征在于“信号”细胞（如内皮细胞）和“应答”细胞（如嗜中性粒细胞和单核细胞）之间的多步分子相互作用。在第一步中，由信号细胞产生的选择素介导炎症部位反应细胞的束缚。随后，信号细胞表达的额外介质激活束缚的响应细胞。在病理条件下，以不适当的方式调用相同的机制：（1）通过选择素在细胞表面上的延长呈递和（2）通过模拟正常二级信号分子血小板活化因子（PAF）的氧化磷脂的不受调节的产生。PAF乙酰水解酶（PAF-AH）使PAF和氧化磷脂失活，并构成抑制炎症的“关闭”开关。正常PAF-AH功能的抑制或PAF-AH基因的失活突变可导致对炎性疾病的易感性增加。这些研究与动脉粥样硬化和血栓形成有关，因为炎症是两者的中心特征。
The inflammatory response is characterized by a multistep molecular interaction between "signaling" cells, such as endothelial cells, and "responding" cells, such as neutrophils and monocytes. In the first step, selectins produced by signaling cells mediate the tethering of responding cells at sites of inflammation. Subsequently, an additional mediator expressed by signaling cells activates the tethered responding cells. Under pathological conditions, the same mechanism is invoked in inappropriate ways: (1) by prolonged presentation of selectins on the cell surface and (2) by the unregulated production of oxidized phospholipids that mimic the normal secondary signaling molecule, platelet-activating factor (PAF). The enzyme PAF acetylhydrolase (PAF-AH) inactivates PAF and oxidized phospholipids and constitutes an "off" switch that suppresses inflammation. Inhibition of normal PAF-AH function or inactivating mutations of the PAF-AH gene can lead to increased susceptibility to inflammatory disease. These studies have relevance to atherosclerosis and thrombosis, because inflammation is a central feature of both.