Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal-Induced Inflammatory Responses by Reducing Complement Activation

J Immunol. 2015 Jul 1;195(1):257-64. doi: 10.4049/jimmunol.1403044. Epub 2015 May 29.

Abstract

Chronic inflammation of the arterial wall is a key element in the development of atherosclerosis, and cholesterol crystals (CC) that accumulate in plaques are associated with initiation and progression of the disease. We recently revealed a link between the complement system and CC-induced inflammasome caspase-1 activation, showing that the complement system is a key trigger in CC-induced inflammation. HDL exhibits cardioprotective and anti-inflammatory properties thought to explain its inverse correlation to cardiovascular risk. In this study, we sought to determine the effect of reconstituted HDL (rHDL) on CC-induced inflammation in a human whole blood model. rHDL bound to CC and inhibited the CC-induced complement activation as measured by soluble terminal C5b-9 formation and C3c deposition on the CC surface. rHDL attenuated the amount of CC-induced complement receptor 3 (CD11b/CD18) expression on monocytes and granulocytes, as well as reactive oxygen species generation. Moreover, addition of CC to whole blood resulted in release of proinflammatory cytokines that were inhibited by rHDL. Our results support and extend the notion that CC are potent triggers of inflammation, and that rHDL may have a beneficial role in controlling the CC-induced inflammatory responses by inhibiting complement deposition on the crystals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Cells / cytology
  • Blood Cells / drug effects
  • Blood Cells / immunology
  • CD11b Antigen / immunology
  • CD18 Antigens / immunology
  • Cholesterol / adverse effects*
  • Complement Activation / drug effects*
  • Complement C3c / antagonists & inhibitors
  • Complement C3c / immunology
  • Complement Membrane Attack Complex / antagonists & inhibitors
  • Complement Membrane Attack Complex / immunology
  • Crystallization
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Lipoproteins, HDL / pharmacology*
  • Primary Cell Culture
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / immunology

Substances

  • CD11b Antigen
  • CD18 Antigens
  • Complement Membrane Attack Complex
  • ITGAM protein, human
  • Lipoproteins, HDL
  • Reactive Oxygen Species
  • Complement C3c
  • Cholesterol