Lipopolysaccharide induces scavenger receptor A expression in mouse macrophages: A divergent response relative to human THP-1 monocyte/macrophages

Michael L. Fitzgerald, Kathryn J. Moore, Mason W. Freeman, Guy L. Reed

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Gene deletion studies indicate that the macrophage scavenger receptor A (SR-A) protects mice from LPS-induced endotoxemia. Paradoxically, cultured human monocyte-derived macrophages down-regulate SR-A expression when exposed to LPS. We found that human THP-1 monocyte/macrophages decrease SR-A expression in response to LPS independent of their differentiation status. In contrast, primary and elicited mouse peritoneal macrophages as well as the J774A.1 and RAW264.7 mouse macrophage lines increase SR-A expression in response to LPS. Exposure to LPS caused J774A.1 and RAW264.7 cells to increase SR-A transcripts by 3- and 5-fold, respectively. LPS caused a concomitant 3-fold increase in SR-A protein levels and increased cell membrane expression of the receptor. RAW264.7 cells increased SR-A transcript levels in response to LPS at concentrations as low as 1 ng/ml, and the response was saturated at 10 ng/ml. The LPS induction of SR-A transcripts required continual protein synthesis and began at 8 h, peaked by 16 h, and persisted for at least 48 h. LPS induction did not increase SR-A gene transcription or affect alternative transcript splicing, but mildly increased mature transcript stability and proceeded in the presence of actinomycin D. Finally, treatment of RAW264.7 cells with TNF-α did not induce SR-A transcript levels, indicating that a TNF-α autocrine/paracrine signaling mechanism alone is not sufficient to recapitulate the LPS induction of SR-A transcripts. The induction of SR-A expression by LPS-stimulated mouse macrophages is the opposite of the down-regulation of SR-A reported in human monocyte-derived macrophages and may have implications for the observed resistance mice show toward endotoxemia.

Original languageEnglish (US)
Pages (from-to)2692-2700
Number of pages9
JournalJournal of Immunology
Volume164
Issue number5
DOIs
StatePublished - Mar 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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