Iki S, Yuo A, Yagisawa M, Inuo E K, Inoue Y, Usuki K, Urabe A, Suzuki K, Kitagawa S, Togawa A, Takaku F
Department of Hematology, International Medical Center of Japan, Tokyo, Japan.
Exp Hematol. 1997 Jan;25(1):26-33.
The neutrophil superoxide (O2-)-producing capacity in 57 patients with chronic myeloproliferative disorders (MPDs) and eight patients with chronic myelomonocytic leukemia (CMML) was investigated. O2- release in neutrophils stimulated by chemotactic peptide was markedly increased in all types of chronic MPD, including chronic myelogenous leukemia in both chronic phase and blastic crisis, polycythemia vera, and essential thrombocythemia, but was normal in CMML, which is thought to be a myelodysplastic disorder rather than MPD. Increase in O2(-)-producing capacity in MPD was also observed when other receptor-mediated agonists such as interleukin-8 and concanavalin A were used, but not when phorbol ester, a direct activator of protein kinase C, was used as the triggering agonist of O2- release. Priming effects of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), and tumor necrosis factor (TNF) on chemotactic peptide-induced O2- release was observed in all patients with MPD and CMML, though fold enhancement of priming effects was much less in MPD compared with normal subjects. In addition, the priming effects of TNF were less than those of GM-CSF in 10 cases, whereas the priming effects of TNF were consistently and markedly greater than those of GM-CSF in normal subjects. Tyrosine phosphorylation of 42-kDa protein stimulated by G-CSF, GM-CSF, and TNF was observed in CML neutrophils to be identical to that in normal neutrophils. Present results indicate specific potentiation of the receptor-mediated route of signaling that is linked to the respiratory burst and downregulated responsiveness to cytokines in neutrophils in patients with all types of chronic MPD, suggesting in vivo priming of patient neutrophils via certain mechanism by cytokines or related stimuli in these hematological disorders.
对57例慢性骨髓增殖性疾病（MPD）患者和8例慢性粒单核细胞白血病（CMML）患者的中性粒细胞超氧化物（O2-）生成能力进行了研究。在所有类型的慢性MPD中，包括慢性期和急变期的慢性粒细胞白血病、真性红细胞增多症和原发性血小板增多症，趋化肽刺激的中性粒细胞中O2-释放均显著增加，但在CMML中正常，CMML被认为是一种骨髓增生异常综合征而非MPD。当使用白细胞介素-8和伴刀豆球蛋白A等其他受体介导的激动剂时，MPD中O2-生成能力也增加，但当使用佛波酯（蛋白激酶C的直接激活剂）作为O2-释放的触发激动剂时则未增加。在所有MPD和CMML患者中均观察到粒细胞集落刺激因子（G-CSF）、粒细胞巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子（TNF）对趋化肽诱导的O2-释放的预激作用，尽管与正常受试者相比，MPD中预激作用的增强倍数要小得多。此外，在10例患者中，TNF的预激作用小于GM-CSF，而在正常受试者中，TNF的预激作用始终且显著大于GM-CSF。在慢性粒细胞白血病中性粒细胞中观察到，G-CSF、GM-CSF和TNF刺激的分子量42-kDa蛋白的酪氨酸磷酸化与正常中性粒细胞中的相同。目前的结果表明，在所有类型的慢性MPD患者中，与呼吸爆发相关的受体介导信号途径存在特异性增强，而中性粒细胞对细胞因子的反应性下调，提示在这些血液系统疾病中，细胞因子或相关刺激通过某种机制在体内对患者中性粒细胞进行了预激。
