Fas/Fas-ligand expressions in peripheral-blood mononuclear cells of patients with myelodysplastic syndromes.
Increased expressions of Fas and Fas-ligand (Fas-L) in bone marrow cells of myelodysplastic syndromes (MDS) have been reported, and large number of these "cell-death signals" might explain molecular basis for exacerbation of apoptosis in marrow cells of these syndromes. However, expression of these molecules or progression of apoptosis in peripheral-blood mononuclear cells (PBMCs) in MDS has little been investigated. In the present study, we compared expression of these cell-death molecules and percentages of apoptotic cells in PBMCs between MDS patients and healthy subjects. PBMCs were obtained from 7 MDS patients and 8 age-matched healthy controls. Five out of 7 patients were MDS with refractory anemia (RA) type, while the other 2 were MDS-RA with excess of blasts (MDS-RAEB) type. Percentages of PBMCs expressing Fas, Fas-L, and phosphatidylserine as a cell apoptosis-marker were determined by staining cells with FITC-labeled anti-CD95 (Fas) antibody, biotinyl anti Fas-L antibody, and annexin V, respectively. The cells were subsequently analyzed with flow cytometry. The mean (SD) percentage of Fas-expressing PBMCs in MDS group was 55.3 (13.9), whereas the value in healthy subjects was 30.6 (8.8) %, and thus the ratio of Fas positive cells in PBMCs of MDS was significantly higher than that of healthy subjects (p < 0.002). In contrast, the mean (SD) of Fas-L expressing PBMCs in MDS (n=5) was 18.4 (12.2) %, which was significantly lower (p < 0.02) than that in healthy subjects (34.4 +/- 8.1%; n=7). The mean (SD) of apoptotic PBMCs detected as annexin V-positive, non-necrotic cells in MDS (n=7) was 23.3 (7.5) %, which was not significantly different from that in healthy subjects (22.2 +/- 7.8%; n=8). Thus, PBMCs in MDS express high levels of Fas, whereas they conversely exhibit low levels of Fas-L, which may result in prevention of apoptosis by the death signals, and in cell-survival in these cells.
Hirano
Toshihiko
T
Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan. hiranot@ps.toyaku.ac.jp
Hiratsuka
Noriko
N
Iwahori
Tohru
T
Oka
Kitaro
K
Wakasugi
Kazunori
K
D000368:Aged; D017209:Apoptosis; D016022:Case-Control Studies; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins