Receptor-mediated Modulation of Human Monocyte, Neutrophil, Lymphocyte, and Platelet Function by Phorbol Diesters
Receptor-mediated Modulation of Human Monocyte, Neutrophil, Lymphocyte, and Platelet Function by Phorbol Diesters
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佛波二酯对人单核细胞、中性粒细胞、淋巴细胞和血小板功能的受体介导调节
DOI：
10.1172/jci110665
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发表时间：
1982
影响因子：
15.9
通讯作者：
Weinberg Jb
中科院分区：
文献类型：
--
作者：
Goodwin Bj;Weinberg Jb
：促进肿瘤的佛波二酯通过与细胞受体明显相互作用，在体外引起正常和白血病血细胞的多种反应。生物活性配体 [20-(3)H] 佛波醇 12,13-二丁酸酯 ([(3)H]PDBu) 特异性结合完整的人淋巴细胞、单核细胞、多形核白细胞 (PMN) 和血小板，但不结合红细胞。所有四种血细胞类型的结合在 23 摄氏度和 37 摄氏度下迅速发生，在 20-30 分钟内达到最大值，通常随后在接下来的 30-60 分钟内细胞相关放射性降低 30-40%。结合的时间进程取决于温度，4℃下120-150分钟后发生平衡结合，在此温度下细胞相关放射性没有随后损失。可以通过添加未标记的 PDBu 来洗脱结合的 [(3)H]PDBu。 Scatchard 对 4°C 结合研究数据的分析揭示了这些细胞类型中高亲和力受体的线性图，其中淋巴细胞的解离常数和每个细胞的受体为 60 nM 和 7.8 x 10(5)/细胞，单核细胞为 51 nM 和 15.5 x 10(5)/细胞，PMN 为 38 nM 和 4.0 x 10(5)/细胞，以及 19 nM 和 19 nM。血小板 2.9 x 10(4)/细胞。使用未标记的佛波醇相关化合物进行的结构-活性研究表明，它们抑制 [(3)H]PDBu 与细胞结合的能力与诱导细胞反应（单核细胞和 PMN H(2)O(2) 分泌、淋巴细胞 (3)HTdR 掺入和血小板氚化血清素释放）的能力之间存在密切相关性；佛波醇和 4-α 佛波醇无活性，而佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA)、PDBu、mezerein 和佛波醇 12,13-二乙酸酯（按效力递减顺序）抑制 [(3)H]PDBu 结合并引发各种反应。因此，这些存在于单核细胞、淋巴细胞、PMN和血小板上的佛波二酯的高亲和力、特异性受体介导由这些配体诱导的多型效应。
: The tumor promoting phorbol diesters elicit a variety of responses from normal and leukemic blood cells in vitro by apparently interacting with cellular receptors. The biologically active ligand [20-(3)H] phorbol 12,13-dibutyrate ([(3)H]PDBu) bound specifically to intact human lymphocytes, monocytes, polymorphonuclear leukocytes (PMN), and platelets, but not to erythrocytes. Binding, which was comparable for all four blood cell types, occurred rapidly at 23 degrees and 37 degrees C, reaching a maximum by 20-30 min usually followed by a 30-40% decrease in cell associated radioactivity over the next 30-60 min. The time course for binding was temperature dependent with equilibrium binding occurring after 120-150 min at 4 degrees C, with no subsequent loss of cell-associated radioactivity at this temperature. Bound [(3)H]PDBu could be eluted by addition of unlabeled PDBu. Scatchard analysis of data from 4 degrees C binding studies revealed linear plots with high affinity receptors in these cell types with dissociation constants and receptors per cell of 60 nM and 7.8 x 10(5)/cell for lymphocytes, 51 nM and 15.5 x 10(5)/cell for monocytes, 38 nM and 4.0 x 10(5)/cell for PMN, and 19 nM and 2.9 x 10(4)/cell for platelets. Structure-activity studies using unlabeled phorbol-related compounds demonstrated a close correlation between their abilities to inhibit binding of [(3)H]PDBu to cells and their abilities to induce cellular responses (monocyte and PMN H(2)O(2) secretion, lymphocyte (3)HTdR incorporation, and platelet tritiated serotonin release); phorbol and 4-alpha phorbol were inactive while phorbol 12-myristate 13-acetate (PMA), PDBu, mezerein, and phorbol 12,13-diacetate (in decreasing order of potency) inhibited [(3)H]PDBu binding and elicited the various responses. Thus, these high affinity, specific receptors for the phorbol diesters, present on monocytes, lymphocytes, PMN, and platelets, mediate the pleiotypic effects induced by these ligands.