Desialylation is associated with apoptosis and phagocytosis of platelets in patients with prolonged isolated thrombocytopenia after allo-HSCT

摘要: Prolonged isolated thrombocytopenia (PT) is a frequent complication in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it associated with an adverse prognosis. In this study, we hypothesized that desialylation on platelet surfaces was PT after allo-HSCT. The mechanisms participating process may include NEU1 translocation, apoptosis, phagocytosis by macrophages. defined as peripheral count less than 100 × 109/L without sustained anemia or leukopenia for more 3 months 34 were identified consecutively from cohort of 255 underwent allo-HSCT hematologic malignancies between May October 2014 at Peking University Institute Hematology. Desialylation, enzyme expression, detected using flow cytometry, immunofluorescence, RT-PCR, Western blot, so on. Platelets the had significantly fewer sialic acids (P = .001) increased β-galactose exposure indicative surface (P = .042), serum showed higher acid concentration (8.400 ± 0.2209 μmol/L, P < .001). sialidase over-expressed mRNA to protein levels, its catalytic activity platelets patients. Desialylation GPIbα correlated changes 14-3-3ζ distribution, which, relative Bad activation, modulated expression Bcl-2 family proteins, depolarized inner membrane mitochondria, initiated intrinsic mitochondria-dependent pathway apoptosis. Macrophages derived THP-1 line preferred phagocytize desialylated vitro. We also revealed oseltamivir (400 μmol/L) could inhibit 50 % protect 20 % vitro. apoptosis phagocytosis, whereas reduce destruction periphery, indicating potential novel treatment