Abstract
The anti-inflammatory properties of high-density lipoproteins (HDL) are lost in uremia. These HDL may show pro-inflammatory features partially as a result of changed protein composition. Alterations of polymorphonuclear leukocytes (PMNLs) in chronic kidney disease (CKD) may contribute to chronic inflammation and high vascular risk. We investigated if HDL from uremic patients is related to systemic inflammation by interfering with PMNL function. PMNL apoptosis was investigated by assessing morphological features and DNA content. CD11b surface expression was quantified by flow cytometry. Oxidative burst was measured via cytochrome c reduction assay. Chemotaxis was assessed by using an under-agarose migration assay. We found that HDL from CKD and hemodialysis (HD) patients significantly attenuated PMNL apoptosis, whereas HDL isolated from healthy subjects had no effect on PMNL apoptosis. The use of signal transduction inhibitors indicated that uremic HDL exerts anti-apoptotic effects by activating pathways involving phosphoinositide 3-kinase and extracellular-signal regulated kinase. Healthy HDL attenuated the surface expression of CD11b, whereas HDL from CKD and HD patients had no effect. All tested isolates increased the stimulation of oxidative burst, but did not affect PMNL chemotactic movement. In conclusion, HDL may contribute to the systemic inflammation in uremic patients by modulating PMNL functions.