Induction of apoptosis in CD34+ cells by sera from patients with aplastic anemia.
To investigate the pathogenesis of aplastic anemia (AA), the apoptosis of CD34+ cells was assayed with annexin V-fluorescein 24 hr and 48 hr after incubation with the serum of normal controls (n = 10), patients with non severe AA (NSAA, n = 13) and severe AA (SAA, n = 10). The CD34+ progenitors from the bone marrow of normal donors contained a significantly greater proportion of apoptotic cells after incubation with serum from SAA patients than that incubated with serum from normal controls and NSAA. Moreover, the percent apoptosis of CD34+ cells after 24 hr incubation with serum from NSAA was slightly higher than that of normal controls. This appears to be related to clinical severity. No significant difference was found in the percent apoptosis of CD34+ cells between incubation for 24 hr and 48 hr with the same serum. To further explore the mechanism of increased apoptosis induced by the serum of AA patients, the expression of the Fas receptor was measured after incubation with serum from the normal controls and AA patients using flow cytometry. After incubation with serum from the AA patients, the Fas receptor was overexpressed, correlating with the increased apoptosis induced by the same serum from AA patients. In addition, the induction of apoptosis and Fas expression on CD34+ cells by serum from the SAA patients was blocked partly by preincubation of the serum with anti-gamma-IFN neutralizing MoAb. These findings suggested that some aberrant components of the serum in the AA patients, which was confirmed partly to be gamma-IFN, can induce CD34+ progenitors apoptosis through the Fas signaling pathway. This may contribute to understanding the decreased number of stem cells characteristic of aplastic anemia.
Liu
H
H
Department of Cancer Cytogenetics, Hiroshima University, Japan.
Mihara
K
K
Kimura
A
A
Tanaka
K
K
Kamada
N
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood*; D018952:Antigens, CD34; D017209:Apoptosis; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D015398:Signal Transduction; D019014:fas Receptor
D018952:Antigens, CD34; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D007371:Interferon-gamma