Apolipoprotein A-I decreases neutrophil degranulation and superoxide production.
Apolipoprotein A-I decreases neutrophil degranulation and superoxide production.
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发表时间：
1991-12
影响因子：
6.5
通讯作者：
W. Blackburn;J. Dohlman;Y. Venkatachalapathi;D. Pillion;W. Koopman;J. Segrest;G. Anantharamaiah
中科院分区：
文献类型：
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作者：
W. Blackburn;J. Dohlman;Y. Venkatachalapathi;D. Pillion;W. Koopman;J. Segrest;G. Anantharamaiah
中性粒细胞参与急性期反应，并且通常与许多炎性疾病中的组织损伤相关。急性期反应伴随着载脂蛋白A-I和高密度脂蛋白（HDL）代谢的改变。结构上的考虑导致了研究纯化的HDL和载脂蛋白A-I对中性粒细胞脱粒和超氧化物产生的影响。载脂蛋白A-I，但不是HDL抑制IgG诱导的中性粒细胞活化约60%，测定脱粒和超氧化物的产生。这表明载脂蛋白A-I的脂质缔合两亲性螺旋结构域介导了这种效应。支持这一点的是发现两种合成模型脂质缔合两亲性螺旋肽类似物的抑制作用。载脂蛋白A-I，含有串联重复的两亲性螺旋结构域，比两种肽类似物有效约10倍，并在远低于生理浓度下抑制中性粒细胞活化。竞争结合研究表明，静息中性粒细胞每个细胞约有190，000个（Kd = 1.7 × 10 - 7）载脂蛋白A-I结合位点，与配体-受体相互作用一致。这些观察结果表明，载脂蛋白A-I可能在炎症反应过程中调节中性粒细胞功能发挥重要作用。
Neutrophils participate in the acute phase response and are often associated with tissue injury in a number of inflammatory disorders. The acute phase response is accompanied by alterations in the metabolism of apolipoprotein A-I and high density lipoprotein (HDL). Structural considerations led to studies investigating the effect of purified HDL and apolipoprotein A-I on neutrophil degranulation and superoxide production. Apolipoprotein A-I but not HDL inhibited IgG-induced neutrophil activation by about 60% as measured by degranulation and superoxide production. This suggests that the lipid-associating amphipathic helical domains of apolipoprotein A-I mediate this effect. In support of this was finding inhibitory effects with two synthetic model lipid-associating amphipathic helix peptide analogs. Apolipoprotein A-I, containing tandem repeating amphipathic helical domains, was approximately ten times more effective than the two peptide analogs and inhibited neutrophil activation at well below physiologic concentrations. Competitive binding studies indicate that resting neutrophils have approximately 190,000 (Kd = 1.7 x 10(-7)) binding sites per cell for apolipoprotein A-I, consistent with a ligand-receptor interaction. These observations suggest that apolipoprotein A-I may play an important role in regulating neutrophil function during the inflammatory response.