Effect of High-Density Lipoprotein from Healthy Subjects and Chronic Kidney Disease Patients on the CD14 Expression on Polymorphonuclear Leukocytes.

Gerald Cohen

doi:10.3390/ijms22062830

Abstract

In uremic patients, high-density lipoprotein (HDL) loses its anti-inflammatory features and can even become pro-inflammatory due to an altered protein composition. In chronic kidney disease (CKD), impaired functions of polymorphonuclear leukocytes (PMNLs) contribute to inflammation and an increased risk of cardiovascular disease. This study investigated the effect of HDL from CKD and hemodialysis (HD) patients on the CD14 expression on PMNLs. HDL was isolated using a one-step density gradient centrifugation. Isolation of PMNLs was carried out by discontinuous Ficoll-Hypaque density gradient centrifugation. CD14 surface expression was quantified by flow cytometry. The activity of the small GTPase Rac1 was determined by means of an activation pull-down assay. HDL increased the CD14 surface expression on PMNLs. This effect was more pronounced for HDL isolated from uremic patients. The acute phase protein serum amyloid A (SAA) caused higher CD14 expression, while SAA as part of an HDL particle did not. Lipid raft disruption with methyl-β-cyclodextrin led to a reduced CD14 expression in the absence and presence of HDL. HDL from healthy subjects but not from HD patients decreased the activity of Rac1. Considering the known anti-inflammatory effects of HDL, the finding that even HDL from healthy subjects increased the CD14 expression was unexpected. The pathophysiological relevance of this result needs further investigation.

Highlights

Besides the typical role in reverse cholesterol transport [1], high-density lipoprotein (HDL) has strong anti-inflammatory, anti-oxidative and antithrombotic effects [2], which contribute to immunoregulation [3,4] and a reduced cardiovascular risk [5,6]
The acute phase protein serum amyloid A (SAA), which induces the expression of inflammatory cytokines in human monocytes, is enriched HDL isolated from chronic kidney disease (CKD) patients and patients undergoing HD treatment [10]
At 100 μg/mL, the CD14 expression was higher for HDL from CKD- and HD patients compared to healthy subjects (HS)-HDL

Summary

Introduction

Besides the typical role in reverse cholesterol transport [1], high-density lipoprotein (HDL) has strong anti-inflammatory, anti-oxidative and antithrombotic effects [2], which contribute to immunoregulation [3,4] and a reduced cardiovascular risk [5,6]. Polymorphonuclear leukocytes (PMNLs) are cells of the non-specific immune defense. HDL of CKD and HD patients significantly reduced PMNL apoptosis, an effect that is typically observed with pro-inflammatory substances [12]. HDL from healthy subjects reduced the activation of CD11b surface expression on PMNLs, a first step of the pathogenesis of vascular damage [13,14], whereas HDL from CKD and HD patients did not have this effect. These results suggest that HDL may exacerbate systemic inflammation in uremia

Methods

Results

Conclusion