Apoptotic effects of heparin on lymphoblasts, neutrophils, and mononuclear cells: Results of a preliminary in vitro study

Abstract

In this study the apoptotic effects of heparin on lymphoblasts, neutrophils, and mononuclear cells were evaluated by flow cytometry for detection of sub-G 1 peak, in vitro. Ten children with acute lymphoblastic leukemia (ALL) at diagnosis (Group I), six children with ALL at relapse (Group II), and 10 healthy children (controls) were included in this study. Lymphoblasts in ALL patients, and neutrophils and mononuclear cells in controls, were incubated in increasing heparin concentrations (0, 5, 10, 20 U/ml). Flow cytometric analyses were performed at 0, 1, and 2 hours of incubation in heparin for determination of the apoptotic effects of heparin. In Group I apoptosis was detected in all different levels of heparin concentration except 0 U/ml at 0, 1, and 2 hours. The apoptotic effects of heparin on blast cells peaked at the first hour in 5-, 10-, and 20-U/ml heparin concentrations (p < 0.0001). In Group II similar findings were observed only at zero hour and apoptosis was higher than those in Group I except in 5-U/ml heparin concentration (p < 0.001). Apoptosis was found to increase with heparin levels in both groups (p < 0.02). In the control group, apoptosis was detected only at the 20-U/ml heparin concentration and only at the first and second hours. Lymphoblasts are more sensitive to apoptotic effects of heparin than either neutrophils and mononuclear cells (p < 0.004). It can be suggested that low-dose heparin may cause significant apoptosis of lymphoblasts while inducing no apoptosis on neutrophils and mononuclear cells. The findings of this preliminary study indicate that further and more comprehensive research on the apoptotic effect of heparin on lymphoblasts should be done. Am. J. Hematol. 61:90-93, 1999.

The effect of heparin on the cell cycle in human B-lymphoblasts: An in vitro study

“…We demonstrated in this study that the greatest proliferation effect of heparin and the highest SPF ratio were determined in 20 U/ml concentration at 1 h. Recent studies from Erduran et al [30] determined that the greatest apoptotic effect of heparin on the lymphoblasts was detected in 20 U/ml concentration at 1 h. The results of some recent studies were found to be concordant [28][29][30]. Apoptosis and proliferation are important regulators of normal development and homeostasis in the bone marrow.…”

“…On the other hand, heparin causes apoptosis in human peripheral blood neutrophils, lymphoblasts and mononuclear cells, and indicates its apoptotic effect on lymphoblasts via extrinsic or intrinsic pathways [27][28][29]. We demonstrated in this study that the greatest proliferation effect of heparin and the highest SPF ratio were determined in 20 U/ml concentration at 1 h. Recent studies from Erduran et al [30] determined that the greatest apoptotic effect of heparin on the lymphoblasts was detected in 20 U/ml concentration at 1 h. The results of some recent studies were found to be concordant [28][29][30].…”

Efeito do tempo de conservação de polimorfonucleares do sangue de bezerros sobre o metabolismo oxidativo e a atividade de fagocitose de Escherichia coli

“…Em contrapartida, Erduran et al 17 , verificaram apoptose dos neutrófilos após uma hora de ensaio quando usadas doses altas de heparina (20 U/ml).…”

Stimulation of Fas agonistic antibody–mediated apoptosis by heparin-like agents suppresses Hsp27 but not Bcl-2 protective activity

“…They were also rather ineffective when other cell death inducers were considered, excepted in the case of TRAIL. Hence, our findings are in agreement with earlier studies showing that, depending on the cell context, heparin-like molecules can either protect (Ishikawa and Kitamura 1999) or stimulate (Erduran et al 1999) apoptosis or inflammatory angiogenesis by local stimulation of Fas (Biancone et al 1997).…”