GENE EXPRESSIONS DURING PROLIFERATION AND DIFFERENTIATION OF MYELOID CELIS IN SEVERE CONCENITAL NEUTROPENIA

严重先天性中性粒细胞减少症骨髓细胞增殖和分化过程中的基因表达

• 批准号: 13670806
• 负责人: KOBAYASHI Masao
• 金额: $ 0.83万
• 依托单位: HIROSHIMA UNICERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670806/
• 关键词: Sever congenital neutropenia; Myeloid proliferation; Gene expression; Neutrophil elastase; Primary granules; 顆粒蛋白; 骨髄顆粒球系前駆細胞; G-CSF受容体

Recently, mutations in the neutrophil elastase (NE) gene, ELA2, have been reported in patients with severe congenital Neutrogena (SCN). We studied the expression of granule constituent genes in primitive myeloid progenitor cells during proliferation and differentiation in patients with SCN. Primitive myeloid cells in the bone marrow were purified based on the expression of CD34 and G-CSF receptor (G-CSFR). The CD34^+ / G-CSFR^+ cells, but not the CD34^+ / G-CSFR cells, of SCN patients showed a reduced number of GM-colony formation and defectives proliferation in response to G-CSF alone and to the combinations of hematopoietic factors in serumdeprived culture. The CD34^+ / G-CSFR^+ cells expressed low levels of the granule constituent mRNAs. The transcription levels of primary granule enzyme genes were gradually enhanced and then decreased when cells were induced toward myeloid lineage in the presence of G-CSF in normal subjects. However, the up-regulation of the transcription in the early stage of proliferation of SCN patients was significantly lower than those of normal subjects. Furthermore, the down-regulation of these enzyme transcriptions was not clearly observed in SCN patients. No differences in the expressions of lactoferrin gene were seen between normal subjects and patients with SCN. These results suggest that the abnormal regulation of the transcription in primary granule consitituents may play a potential role in the defective proliferation and differentiation of myeloid lineage in patients with SCN.

最近，中性粒细胞弹性酶（NE）基因ELA2突变在严重先天性露血病（SCN）患者中被报道。我们研究了SCN患者原始髓系祖细胞在增殖和分化过程中颗粒成分基因的表达。基于CD34和G-CSF受体（G-CSFR）的表达纯化骨髓原始髓细胞。SCN患者的CD34^+ / G-CSFR^+细胞，而不是CD34^+ / G-CSFR细胞，在单独G-CSF和血清剥夺培养中对造血因子组合的反应中，显示出gm集落形成数量减少和缺陷增殖。CD34^+ / G-CSFR^+细胞表达低水平的颗粒成分mrna。在G-CSF存在的情况下，将细胞诱导成髓系时，原粒酶基因的转录水平先升高后降低。然而，SCN患者在增殖早期的转录上调明显低于正常受试者。此外，在SCN患者中没有明显观察到这些酶转录的下调。正常受试者与SCN患者乳铁蛋白基因表达无差异。这些结果表明，原发性颗粒成分转录的异常调节可能在SCN患者髓系增殖和分化缺陷中发挥潜在作用。

项目成果

Rokuro Hagimoto, Masao Kobayashi, et al.: "A possible role of the maternal anti-HLA antibody in a case of alloimmune neonatal neutropenia"TRANSFUSION. 41. 615-620 (2001)

Rokuro Hagimoto、Masao Kobayashi 等人：“母体抗 HLA 抗体在同种免疫新生儿中性粒细胞减少症中的可能作用”输血。

Masao Kobayashi, Kazuhiro Nakamura, et al.: "Significance of the detection of antineutrophil antibodies in children with chronic neutropenia"BLOOD. 99(In press). (2002)

Masao Kobayashi、Kazuhiro Nakamura 等人：“慢性中性粒细胞减少症儿童抗中性粒细胞抗体检测的意义”BLOOD。

Kikuyo Taniguchi, Masao Kobayashi, et al.: "Human neutrophil antigen-2a expression of neutrophils from healthy adults in western Japan"TRANSFUSION. 44(In press). (2002)

Kikuyo Taniguchi、Masao Kobayashi 等人：“日本西部健康成人中性粒细胞的人类中性粒细胞抗原 2a 表达”输血。

Hagimoto R, et al.: "A possible role of the maternal anti-HLA antibody in a case of alloimmune neonatal neutropenia"Transfusion. 41. 615-620 (2001)

Hagimoto R 等人：“母体抗 HLA 抗体在同种免疫新生儿中性粒细胞减少症中的可能作用”输血。

Kobayashi M, et al.: "Significance of the detection of antineutrophil antibodies in children with chronic neutropenia"Blood. 99. 3648-3471 (2002)

Kobayashi M 等人：“慢性中性粒细胞减少症儿童抗中性粒细胞抗体检测的意义”血液。