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The role of the macrophage scavenger receptor in immune stimulation by bacterial DNA and synthetic oligonucleotides
Author(s) -
Zhu FuGang,
Reich Charles F.,
Pisetsky David S.
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01222.x
Subject(s) - microbiology and biotechnology , biology , spleen , cpg oligodeoxynucleotide , oligonucleotide , cpg site , immune system , flow cytometry , scavenger receptor , dna , cytokine , in vitro , in vivo , receptor , immunology , biochemistry , dna methylation , gene expression , gene , lipoprotein , cholesterol
Summary To assess the role of the macrophage scavenger receptor type A (SRA) in immune activation by CpG DNA, cytokine induction and DNA uptake were tested in vitro and in vivo using SRA knockout (SRA −/− ) and wild type (WT) mice. As a source of CpG DNA, Escherichia coli DNA (EC DNA) and a 20‐mer phosphorothioate oligodeoxynucleotide with two CpG motifs (CpG ODN) were used. In vitro , both EC DNA and the CpG ODN induced dose‐dependent increases of interleukin (IL)‐12 production by spleen cells and bone‐marrow‐derived macrophages (BMMΦ) from both SRA −/− and WT mice. The levels of cytokines produced by SRA −/− spleen cells and BMMΦ were similar to those of WT spleen cells and BMMΦ. When injected intravenously with CpG ODN and EC DNA, both SRA −/− and WT mice showed elevated serum levels of IL‐12. To investigate further the role of the SRA, flow cytometry and confocal microscopy were performed to examine the uptake of fluorescently labelled oligonucleotides. SRA −/− and WT BMMΦ showed similarity in the extent of uptake and distribution of oligonucleotides as assessed by these two techniques. Together, these findings indicate that, while the SRA may bind DNA, this receptor is not essential for the uptake of CpG DNA or its immunostimulatory activity.