Lee Jehoon, Kim Yonggoo, Lim Jihyang, Kim Myungshin, Han Kyungja
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, 62 Yeouido-dong Yeongdeungpo-gu, Seoul, 150-713, South Korea.
Ann Clin Lab Sci. 2008 Autumn;38(4):331-7.
Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-CSF (GM-CSF) are the principal cytokines in granulopoiesis and differentiation of granulocytic precursors. Their physiologic effects are mediated by binding to specific cell surface receptors (G-CSFr and GM-CSFr, respectively), which are widely expressed from immature bone marrow cells to mature peripheral granulocytes. The fact that concentrations of plasma G-CSF and GM-CSF and their receptors are changed in infectious diseases showing neutrophilia is known, but such changes in patients with chronic myelogenous leukemia (CML) have not been studied. Based on quantitative assays of plasma G-CSF and GM-CSF and their receptors on the peripheral granulocytes of CML patients and healthy controls, this study analyzes the differences between these groups in G-CSF and GM-CSF levels, as well as quantitative and qualitative changes in the receptors. Plasma levels of G-CSF and GM-CSF were measured in 47 patients in the chronic phase of CML and 25 healthy adults as normal controls. G-CSFr and GM-CSFr on peripheral granulocytes were analyzed by quantitative flow cytometry, and changes in G-CSF and GM-CSF receptor counts were also measured. Plasma concentrations of G-CSF and GM-CSF in CML patients were similar to normal controls (p>0.05). The quantity of G-CSFr on neutrophils was more highly expressed than on other cell types in both groups, and the amount of this receptor in patients with CML was less than in normal controls (p=0.001). GM-CSFr was expressed in higher concentrations on monocytes than neutrophils, and there was no difference in the amount of GM-CSFr on neutrophils. After incubation with excess G-CSF, the expressed amounts of G-CSFr on neutrophils and monocytes were decreased in both groups. However, G-CSFr on the monocytes was decreased in healthy controls (p=0.02) with no difference in patients with CML. The quantities of GM-CSFr expression on neutrophils and monocytes after incubation with excess GM-CSF were decreased in both groups. Granulocyte counts in peripheral blood of CML patients were not correlated with the plasma concentrations of G-CSF or GM-CSF, nor with the expression of G-CSFr or GM-CSFr on granulocytes. Granulopoiesis in patients with CML was not mediated by increased plasma CSF concentrations, and there was no difference in the amounts of G-CSFr or GM-CSFr expressed on the granulocytes. This suggests that a structural change may occur on monocytes of CML patients, since the binding capacity of G-CSFr to G-CSF on the monocytes is different from the normal controls.
粒细胞集落刺激因子（G-CSF）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）是粒细胞生成和粒细胞前体分化过程中的主要细胞因子。它们的生理效应是通过与特定的细胞表面受体（分别为G-CSFr和GM-CSFr）结合来介导的，这些受体在从未成熟骨髓细胞到成熟外周粒细胞中广泛表达。已知在表现为中性粒细胞增多的感染性疾病中，血浆G-CSF和GM-CSF及其受体的浓度会发生变化，但慢性粒细胞白血病（CML）患者的此类变化尚未得到研究。基于对CML患者和健康对照外周粒细胞上血浆G-CSF和GM-CSF及其受体的定量测定，本研究分析了这些组在G-CSF和GM-CSF水平上的差异，以及受体的定量和定性变化。对47例CML慢性期患者和25名健康成年人作为正常对照测定血浆G-CSF和GM-CSF水平。通过定量流式细胞术分析外周粒细胞上的G-CSFr和GM-CSFr，并测定G-CSF和GM-CSF受体数量的变化。CML患者血浆G-CSF和GM-CSF浓度与正常对照相似（p>0.05）。两组中性粒细胞上G-CSFr的表达量均高于其他细胞类型，且CML患者该受体的量低于正常对照（p=0.001）。GM-CSFr在单核细胞上的表达浓度高于中性粒细胞，中性粒细胞上GM-CSFr的量无差异。用过量G-CSF孵育后，两组中性粒细胞和单核细胞上G-CSFr的表达量均降低。然而，健康对照中单核细胞上的G-CSFr降低（p=0.02），CML患者无差异。用过量GM-CSF孵育后，两组中性粒细胞和单核细胞上GM-CSFr的表达量均降低。CML患者外周血粒细胞计数与血浆G-CSF或GM-CSF浓度无关，也与粒细胞上G-CSFr或GM-CSFr的表达无关。CML患者的粒细胞生成不是由血浆CSF浓度升高介导的，粒细胞上G-CSFr或GM-CSFr的量也无差异。这表明CML患者的单核细胞可能发生了结构变化，因为单核细胞上G-CSFr与G-CSF的结合能力与正常对照不同。
