A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection

Nature. 1997 Mar 20;386(6622):292-6. doi: 10.1038/386292a0.

Abstract

Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.

Publication types

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

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / metabolism
  • Arteriosclerosis / blood
  • Arteriosclerosis / immunology*
  • Arteriosclerosis / pathology
  • Cell Adhesion
  • Disease Susceptibility
  • Gene Targeting
  • Herpes Simplex / blood
  • Herpes Simplex / immunology*
  • Lipoproteins, LDL / blood
  • Listeriosis / blood
  • Listeriosis / immunology*
  • Liver / microbiology
  • Liver / pathology
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Scavenger
  • Scavenger Receptors, Class A
  • Spleen / microbiology
  • Spleen / pathology

Substances

  • Apolipoproteins E
  • Lipoproteins, LDL
  • Msr1 protein, mouse
  • Receptors, Immunologic
  • Receptors, Scavenger
  • Scavenger Receptors, Class A