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.
Highlights
High levels of high-density lipoproteins (HDL) are associated with decreased cardiovascular risk [1] related to its diverse biological functions including the efflux of cholesterol from macrophages [2] and potent anti-inflammatory properties [3,4]
We found that HDL from uremic patients significantly differs from HS-HDL; it decreased spontaneous polymorphonuclear leukocytes (PMNLs) apoptosis but had no attenuating effect on the surface expression of CD11b
HDL isolated from stage 3 chronic kidney disease (CKD) patients and HDL isolated from stage 4 CKD patients did not show any statistical difference in their biological effects tested in this study
Summary
High levels of high-density lipoproteins (HDL) are associated with decreased cardiovascular risk [1] related to its diverse biological functions including the efflux of cholesterol from macrophages [2] and potent anti-inflammatory properties [3,4]. After the chemotactic movement to the site of infection, they first ingest the microorganism by phagocytosis and use reactive oxygen metabolites and proteolytic enzymes to kill it. Any disturbance of these essential PMNL functions leads to an increased risk of infection [13].
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