title: The expression of legumain, an asparaginyl endopeptidase that controls antigen processing, is reduced in endotoxin-tolerant monocytes.
abstract: The exposition of monocytes to lipopolysaccharide (LPS) primarily causes a massive inflammatory response that is then followed by a hyporesponsive state of these cells. This latter state is called endotoxin tolerance and is characterized by (i) the attenuated production of proinflammatory mediators after repeated LPS treatment, and (ii) the diminished antigen presentation and T-cell stimulation capacity. The data presented here indicate that LPS priming causes a specific decrease in the expression of legumain (the asparaginyl endopeptidase responsible for the key step in antigen processing) in monocytes. In these cells, the fraction of major histocompatibility complex (MHC) class II loaded with CLIP was increased. In contrast to monocytes, LPS priming provoked an increase of legumain expression in B cells. Reduced monocytic expression of legumain was also found in critically ill patients supporting the suitability of endotoxin tolerance as an experimental model of clinical postinflammatory immunodeficiency.
authors.affiliation: Institute of Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wolk
authors.forename: G
authors.initials: G
authors.lastname: Grütz
authors.forename: K
authors.initials: K
authors.lastname: Witte
authors.forename: H-D
authors.initials: HD
authors.lastname: Volk
authors.forename: R
authors.initials: R
authors.lastname: Sabat
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D001402:B-Lymphocytes / Q000201:enzymology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D004731:Endotoxins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D005802:Genes, MHC Class II / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000201:enzymology*; D000099240:Asparaginyl Endopeptidase
chemical_list: D003546:Cysteine Endopeptidases; D004731:Endotoxins; D000099240:Asparaginyl Endopeptidase