Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils

Abstract

Clearance of neutrophils via apoptosis from the site of infection is crucial for the coordinated resolution of inflammation. The balance between stimulating and attenuating as well as between pro- and anti-apoptotic factors is necessary for maintenance of an effective immune response without the harmful side effects of neutrophil action. This article describes the effect of glucose-modified serum proteins and of free immunoglobulin light chains (IgLCs) on neutrophil functions and apoptosis. Both groups of proteins are found at elevated levels in sera of uremic patients. Glucose-modified proteins increase both the chemotactic movement of neutrophils and the activation of glucose uptake. Spontaneous neutrophil apoptosis is increased in the presence of these modified serum proteins. On the other hand, the presence of free IgLCs, previously shown to diminish neutrophil chemotaxis and the activation of glucose uptake, increase the percentage of viable neutrophils by inhibiting spontaneous apoptotic cell death. We conclude that both glucose-modified proteins and free IgLCs can be considered to be uremic toxins and both contribute to the disturbed immune function in uremic patients. Their concentrations as well as the microenvironment in which they are acting seem to be important for their actual effects.