Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures

J Clin Invest. 1995 Dec;96(6):2758-67. doi: 10.1172/JCI118345.

Abstract

We previously reported that high density lipoprotein (HDL) protects against the oxidative modification of low density lipoprotein (LDL) induced by artery wall cells causing these cells to produce pro-inflammatory molecules. We also reported that enzyme systems associated with HDL were responsible for this anti-inflammatory property of HDL. We now report studies comparing HDL before and during an acute phase response (APR) in both humans and a croton oil rabbit model. In rabbits, from the onset of APR the protective effect of HDL progressively decreased and was completely lost by day three. As serum amyloid A (SAA) levels in acute phase HDL (AP-HDL) increased, apo A-I levels decreased 73%. Concomitantly, paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH) levels in HDL declined 71 and 90%, respectively, from days one to three. After day three, there was some recovery of the protective effect of HDL. AP-HDL from human patients and rabbits but not normal or control HDL (C-HDL) exhibited increases in ceruloplasmin (CP). This increase in CP was not seen in acute phase VLDL or LDL. C-HDL incubated with purified CP and re-isolated (CP-HDL), lost its ability to inhibit LDL oxidation. Northern blot analyses demonstrated enhanced expression of MCP-1 in coculture cells treated with AP-HDL and CP-HDL compared to C-HDL. Enrichment of human AP-HDL with purified PON or PAF-AH rendered AP-HDL protective against LDL modification. We conclude that under basal conditions HDL serves an anti-inflammatory role but during APR displacement and/or exchange of proteins associated with HDL results in a pro-inflammatory molecule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Aorta / cytology
  • Aorta / physiology
  • Aryldialkylphosphatase
  • Base Sequence
  • Cell Adhesion
  • Cells, Cultured
  • Ceruloplasmin / biosynthesis
  • Chemokine CCL2 / biosynthesis
  • Coculture Techniques
  • Croton Oil
  • DNA Primers
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Esterases / metabolism
  • Gene Expression
  • Humans
  • Inflammation / physiopathology*
  • Lipoproteins, HDL / isolation & purification
  • Lipoproteins, HDL / metabolism*
  • Lipoproteins, HDL / pharmacology*
  • Male
  • Molecular Sequence Data
  • Monocytes / cytology
  • Monocytes / physiology
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Oxidation-Reduction
  • Phospholipases A / metabolism
  • Rabbits

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Chemokine CCL2
  • DNA Primers
  • Lipoproteins, HDL
  • Croton Oil
  • Ceruloplasmin
  • Esterases
  • Phospholipases A
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Aryldialkylphosphatase