title: Lipopolysaccharide induces scavenger receptor A expression in mouse macrophages: a divergent response relative to human THP-1 monocyte/macrophages.
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-alpha did not induce SR-A transcript levels, indicating that a TNF-alpha 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.
authors.affiliation: Harvard School of Public Health and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Fitzgerald
authors.forename: K J
authors.initials: KJ
authors.lastname: Moore
authors.forename: M W
authors.initials: MW
authors.lastname: Freeman
authors.forename: G L
authors.initials: GL
authors.lastname: Reed
mesh_terms: D017398:Alternative Splicing / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006207:Half-Life; D006801:Humans; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D013997:Time Factors; D014158:Transcription, Genetic / Q000276:immunology; D015533:Transcriptional Activation / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin