Role of GM-CSF in normalizing the effect of Uremic Toxins on Neutrophil Apoptosis and Function

Abstract

The retention of many uremic compounds, interact negatively with biologic functions. It is the interest of this study to evaluate the influences of uremic plasma from chronic kidney disease (CKD) patients, with and without urinary tract infection (UTI) on neutrophil apoptosis and activation. The effect of hemodialysis (HD), and recombinant human (rh)-GM-CSF addition on mentioned activities were also evaluated. Annexin V and CD18 were studied using flowcytometry in normal neutrophils as an indicator of neutrophil apoptosis and activation respectively; after incubation with plasma from: CKD patients with (12 cases); and without ( 15 cases) UTI, HD patients (15 cases) and 15 healthy control subjects in absence and presence of rh-GM-CSF for 20h. The results revealed significant acceleration of neutrophil apoptosis incubated with uremic plasma from CKD patients with and without UTI compared to those incubated with normal and HD patients' plasma. Neutrophils cultured in presence of CKD patients' plasma with UTI showed significantly increased CD18 expression compared to CKD patients. Also delayed neutrophil apoptosis and; in parallel to increased neutrophil CD18 expression was observed in cells cultured with rh-GM-CSF compared to corresponding cultured cells without rh-GM-CSF in all studied groups. These results indicate that uremic toxins in CKD patients' plasma influence neutrophil survival and function by modulating neutrophil apoptotic cell death and activation. Neutrophils undergoing apoptosis are dysfunctional that may contribute to high prevalence of infections among those patients. rh-GM-CSF down regulated apoptosis and up regulated activation of control neutrophils cultured in presence of uremic plasma.

Keywords

• Neutrophil apoptosis & activation
• Annexin-V
• CD18
• GM-CSF
• CKD
• HD