Chemoattractant receptors on phagocytic cells.

Chemoattractant receptors on phagocytic cells.
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吞噬细胞上的趋化受体。

DOI:
10.1146/annurev.iy.02.040184.001353
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发表时间:
1984
影响因子:
29.7
通讯作者:
Pike,MC
Pike,MC
中科院分区:
医学1区
文献类型:
--
作者:
Snyderman,R;Pike,MC

文献摘要

被引文献

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白细胞上的化学引诱剂受体可以触发许多细胞反应,包括细胞骨架重组、细胞形状改变、定向运动、溶酶体酶分泌和呼吸爆发的激活。诱导运动相关功能所需的化学引诱剂的剂量通常比启动分泌和呼吸爆发活动所需的剂量小至少10倍。这一发现和其他药理学证据清楚地表明,这两种类型的功能(即运动和分泌)是不同的调节,可以通过药物进行不同的修改。寡肽化学引诱物受体对多形核白细胞和巨噬细胞的亲和力是异质的,并受鸟嘌呤核苷酸和先前激动剂暴露的动态调节。寡肽受体的高亲和力和低亲和力形式已通过直接结合研究鉴定。我们的数据表明,低剂量的激动剂可以启动相互转换的低和高亲和力状态的那部分化学引诱受体的鸟嘌呤核苷酸调节。另一方面,足以诱导趋化性脱敏、溶酶体酶分泌和呼吸爆发的高剂量激动剂导致形成新的高亲和力受体群体。这些结合位点对鸟嘌呤核苷酸的作用不敏感,并且似乎被迅速内化。由S-腺苷甲硫氨酸介导的转甲基化反应是激活磷脂酶和通过趋化因子从白细胞释放花生四烯酸所必需的。我们认为,释放花生四烯酸从膜磷脂激活和易位的细胞溶质,但松散的膜相关蛋白激酶C进入膜,这种激酶参与刺激反应耦合的化学引诱物受体。
Chemoattractant receptors on leukocytes can trigger a number of cellular responses, including the cytoskeletal reorganization, changes in cell shape, directed motility, lysosomal enzyme secretion, and activation of the respiratory burst. The dose of chemoattractants required to induce motility-related functions is generally at least ten-fold smaller than the dose required to initiate secretory and respiratory burst activities. This finding and other pharmacological evidence clearly indicate that the two types of functions (ie motility and secretion) are regulated differently and can be divergently modified by drugs. The affinity of the oligopeptide chemoattractant receptor on polymorphonuclear leukocytes and macrophages is heterogeneous and dynamically regulated by guanine nucleotides and prior agonist exposure. High-and low-affinity forms of the oligopeptide receptor have been identified by direct binding studies. Our data suggest that low doses of agonists can initiate interconversion of low-and high-affinity states of that portion of chemoattractant receptors regulated by guanine nucleotides. On the other hand, high doses of agonists sufficient to induce chemotactic desensitization, lysosomal enzyme secretion, and the respiratory burst lead to the formation of a new population of high-affinity receptors. These binding sites are insensitive to the effects of guanine nucleotides and appear to be rapidly internalized. Transmethylation reactions mediated by S-adenosyl methionine are required for the activation of a phospholipase and release of arachidonate from leukocytes by chemotactic factors. We suggest that release of arachidonate from membrane phospholipid activates and translocates a cytosolic but loosely membrane-associated protein kinase C into the membrane and that this kinase participates in stimulus-response coupling of chemoattractant receptors.