Analysis of macrophage scavenger receptor (SR-A) expression in human aortic atherosclerotic lesions

Peter J. Gough*, David R. Greaves, Hiroshi Suzuki, Tomi Hakkinen, Mikko O. Hiltunen, Mikko Turunen, Seppo Ylä Herttuala, Tatsuhiko Kodama, Siamon Gordon

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

131 Scopus citations

Abstract

The class A scavenger receptors (SR-As) are trimeric, integral membrane glycoproteins that exhibit unusually broad ligand-binding properties. A number of studies have suggested that these receptors may play an important role in host defense and in many macrophage-associated pathological processes, including atherosclerosis and Alzheimer's disease. The study of the expression and function of these receptors in human disease has been hampered by the lack of suitable antibodies recognizing human SR-A. This has generated questions regarding the nature of receptors responsible for scavenger receptor activity detected in a variety of cell types, including monocytes, macrophages, smooth muscle cells, and endothelial cells. To address these questions, we have produced high-titer antisera recognizing human SR-A by using mice deficient for SR-A (SR-A -/-). We show that SR-A - /- mice produce a significantly higher-titer immune response than do wild- type (SR-A +/+) littermates, with antisera of the former having a broad species reactivity and recognizing SR-A from humans, mice, and rabbits. The antisera recognize both type I and II SR-A in a wide range of immunological techniques. Using these antisera we show that the expression of SR-A protein is induced during monocyte to macrophage differentiation and that SR-A mediates 80% of the uptake of acetylated low density lipoprotein by human monocyte-derived macrophages. We also establish that human SR-A is expressed by tissue macrophages in liver and lung and by macrophage-derived foam cells within aortic atherosclerotic lesions, with little detectable expression by smooth muscle cells or aortic endothelium.

Original languageEnglish
Pages (from-to)461-471
Number of pages11
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume19
Issue number3
DOIs
StatePublished - 03 1999
Externally publishedYes

Keywords

  • Antibodies
  • Atherosclerosis
  • Knockout mice
  • Macrophages
  • Scavenger receptors

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