Macrophage scavenger receptor A mediates adhesion to apolipoproteins A-I and E

Biochemistry. 2009 Dec 22;48(50):11858-71. doi: 10.1021/bi9013769.

Abstract

Macrophage scavenger receptor A (SR-A) is a multifunctional, multiligand pattern recognition receptor with roles in innate immunity, apoptotic cell clearance, and age-related degenerative pathologies, such as atherosclerosis and Alzheimer's disease. Known endogenous SR-A ligands are polyanionic and include modified lipoproteins, advanced glycation end products, and extracellular matrix proteins. No native plasma ligands have been identified, but it is known that SR-A recognition of unidentified serum components mediates integrin-independent macrophage adhesion, which may drive chronic local inflammation. In this study, we used a high-throughput fractionation and screening method to identify novel endogenous SR-A ligands that may mediate macrophage adhesion. SR-A was found to recognize the exchangeable apolipoproteins A-I and E (apo A-I and apo E, respectively) in both lipid-free and lipid-associated form, suggesting the shared amphipathic alpha-helix as a potential recognition motif. Adhesion of RAW 264.7 macrophages to surfaces coated with apo A-I and apo E4 proved to be integrin-independent and could be blocked by anti-SR-A antibodies. The presence of apo A-I and apo E in pathological deposits, such as atherosclerotic lesions and neurotoxic Alzheimer's plaques, suggests a possible contribution of SR-A-dependent adhesion of macrophages to an inflammatory microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Apolipoprotein A-I / chemistry
  • Apolipoprotein A-I / metabolism*
  • Apolipoproteins E / chemistry
  • Apolipoproteins E / metabolism*
  • Cell Line
  • Humans
  • Ligands
  • Macrophages / chemistry
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Secondary
  • Scavenger Receptors, Class A / chemistry
  • Scavenger Receptors, Class A / deficiency
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / metabolism
  • Scavenger Receptors, Class A / physiology*

Substances

  • APOA1 protein, human
  • Apolipoprotein A-I
  • Apolipoproteins E
  • Ligands
  • MSR1 protein, human
  • Msr1 protein, mouse
  • Scavenger Receptors, Class A