Accelerated neutrophil apoptosis in neutropenic patients with hepatosplenic schistosomiasis is induced by serum Fas ligand

Abstract

Neutropenia in patients with hepatosplenic (HS) schistosomiasis may stem from enhanced neutrophil apoptosis. However, the molecular mechanism of neutrophil apoptosis has not been clearly defined. Neutrophils harvested from neutropenic patients with HS schistosomiasis (n = 25), non-neutropenic patients with hepatointestinal (HI) schistosomiasis (n = 10), and age- and sex-matched healthy control subjects (n = 10) were examined for the degree of apoptosis after incubation with autologous sera. Neutrophil apoptosis was quantified by flow cytometry through determination of propidium iodide nuclear staining and confirmed by DNA gel electrophoresis at 0 time (fresh neutrophil), 4 and 24 h culture. Neutrophils from healthy subjects were also incubated with either 10% heterologous normal or neutropenic serum, with and without anti-Fas ligand antibody. Serum Fas ligand levels were assessed in sera of patient groups and healthy controls by ELISA. Compared with normal controls and HI, HS group demonstrated greater neutrophil apoptosis in the presence of autologous serum (P < 0.01, < 0.05, respectively). Furthermore, compared with normal neutrophils exposed to heterologous normal serum, those exposed to heterologous neutropenic serum exhibited higher apoptosis rates (P < 0.01). The apoptotic effect of neutropenic sera is attenuated by anti-Fas ligand. Fas expression was significantly higher in HS group as compared to both HI and normal healthy controls (P < 0.05). Serum Fas ligand levels were significantly higher among HS group as compared to both HI and control groups (P < 0.01 for both). Neutrophil apoptosis was not correlated to the size of spleen in HS group. In conclusion, the rate of neutrophil apoptosis is accelerated in neutropenic HS schistosomiasis. These findings suggest that enhanced neutrophil apoptosis demonstrated in HS patients is triggered by soluble Fas ligand, which is mostly derived from spleen.

Neutrophil Apoptosis in Neutropenic Patients With Hepatitis C Infection: Role of Caspases 3, 10, and GM-CSF

“…This finding point out for the presence of serum factor in the neutropenic patients sera that induce neutrophils apoptosis. This finding confirm our previous finding but in a cases of schistosomiasis [10].…”

“…PMNs undergo a tightly regulated apoptosis program that allows for timely clearance of PMNs without extravasations of toxic intracellular contents [8,9]. Neutrophil apoptosis was suggested as a cause of neutropenia in advanced liver disease, however, the trigger and the mechanism of accelerated apoptosis remains to be elucidated [10].…”

Aberrant Receptor-Mediated Endocytosis of Schistosoma mansoni Glycoproteins on Host Lipoproteins

“…With the endocytosed lipoproteins, these cells take up large amounts of lipids, giving rise to intracellular accumulation of lipids, shown in Figure 7 C and 7 D both in vitro and in vivo. Damage induced by the lipid accumulation may contribute to neutrophil apoptosis and low neutrophil counts in schistosomiasis patients [ 53 ], supporting immune evasion by the parasite. In support of this, schistosomiasis patient serum promotes neutrophil apoptosis.…”

Caspase‐3 Activation, Bcl‐2 Contents, and Soluble FAS‐Ligand Are Not Related to the Inflammatory Marker Profile in Patients with Sepsis and Septic Shock

“…Indeed sC178 has been described previously to cause neutropenia in septic complications. 7 Also, leukemias express high levels of CD178. 8 The mechanisms involved clearly centralize sCD178 as being more highly expressed in its soluble form in monocytes and in plasma.…”