Tasaka K, Doi M, Nakaya N, Mio M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Mol Pharmacol. 1994 May;45(5):837-45.
Histamine and recombinant granulocyte colony-stimulating factor (rG-CSF) stimulated the differentiation of murine myeloblasts and promyelocytes to mature neutrophils. In connection with this, myeloperoxidase activity of these progenitor cells was decreased by either histamine or rG-CSF treatment. After pretreatment with histamine at 1 microM, both differentiation and the decrease in myeloperoxidase activity of myeloblasts and promyelocytes induced by rG-CSF were significantly augmented. Binding assays using 125I-labeled rG-CSF showed that the number of rG-CSF binding sites on the surface of neutrophil progenitor cells increased after histamine treatment. The histamine-induced increase in rG-CSF binding appeared to be definitely through H2 receptors. Furthermore, the increase in rG-CSF binding sites due to histamine treatment seemed to take place in association with the externalization of G-CSF receptors, because 1) the binding increase was observed in the presence of cycloheximide, 2) no concomitant increase in [3H]leucine uptake was elicited, and 3) colchicine and cytochalasin D effectively prevented the increase in rG-CSF binding due to histamine. In neutrophil progenitors, cAMP contents increased very rapidly and significantly after either histamine or rG-CSF treatment. Moreover, dibutyryl-cAMP increased rG-CSF binding to neutrophil progenitor cells in a dose-dependent fashion. However, when progenitor cells were pretreated with protein kinase A inhibitors, the histamine-induced increase in rG-CSF binding was remarkably decreased. This result seems to indicate that the stimulatory effects of histamine on rG-CSF binding to progenitor cells are intimately related to the cAMP-protein kinase A system in neutrophil progenitors. Moreover, c-myc mRNA expression in neutrophil progenitors was markedly reduced by either histamine or rG-CSF treatment. It was concluded that rG-CSF-induced differentiation of murine neutrophil progenitors was augmented by histamine pretreatment mainly due to an increase in rG-CSF receptors on these cells and this increase might be related to the externalization of rG-CSF receptors.
组胺和重组粒细胞集落刺激因子（rG-CSF）可刺激小鼠成髓细胞和早幼粒细胞分化为成熟中性粒细胞。与此相关的是，组胺或rG-CSF处理均可降低这些祖细胞的髓过氧化物酶活性。用1μM组胺预处理后，rG-CSF诱导的成髓细胞和早幼粒细胞的分化以及髓过氧化物酶活性的降低均显著增强。使用125I标记的rG-CSF进行的结合试验表明，组胺处理后中性粒细胞祖细胞表面的rG-CSF结合位点数量增加。组胺诱导的rG-CSF结合增加似乎肯定是通过H2受体介导的。此外，组胺处理导致的rG-CSF结合位点增加似乎与G-CSF受体的外化有关，因为：1）在存在放线菌酮的情况下观察到结合增加；2）未引起[3H]亮氨酸摄取的同时增加；3）秋水仙碱和细胞松弛素D可有效阻止组胺引起的rG-CSF结合增加。在中性粒细胞祖细胞中，组胺或rG-CSF处理后cAMP含量迅速且显著增加。此外，二丁酰-cAMP以剂量依赖的方式增加rG-CSF与中性粒细胞祖细胞的结合。然而，当祖细胞用蛋白激酶A抑制剂预处理时，组胺诱导的rG-CSF结合增加显著降低。该结果似乎表明，组胺对rG-CSF与祖细胞结合的刺激作用与中性粒细胞祖细胞中的cAMP-蛋白激酶A系统密切相关。此外，组胺或rG-CSF处理均可显著降低中性粒细胞祖细胞中c-myc mRNA的表达。得出的结论是，组胺预处理可增强rG-CSF诱导的小鼠中性粒细胞祖细胞分化，这主要是由于这些细胞上rG-CSF受体的增加，而这种增加可能与rG-CSF受体的外化有关。
