| Serum proteins modulate lipopolysaccharide and lipoteichoic acid-induced activation and contribute to the clinical outcome of sepsis. | |
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MedLine Citation:
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PMID: 22460642 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Bacterial cell wall components, such LPS and LTA, are potent initiators of an inflammatory response that can lead to septic shock. The advances in the past were centered around membrane-bound receptors and intracellular events, but our understanding of the initial interactions of these bacterial components with serum proteins as they enter the bloodstream remain unclear. In this study we identified several serum proteins, which are involved in the innate recognition of bacterial products. Using affinity chromatography and mass spectrometry we performed proteomic analysis of LPS- and LTA-binding serum proteins. We isolated proteins from normal serum that can interact with LPS and LTA. Fluorescent binding experiments and cytokine assays revealed that serum proteins, such as apolipoprotein, LDL, transferrin and holotransferrin could neutralize LPS/LTA binding as well as the subsequent inflammatory response, suggesting that serum proteins modulate LPS/LTA-induced responses. When compared with the proteomic profile of serum from septic patients it was shown that these proteins were in lower abundance. Investigation of serum proteins in 25 critically ill patients with a mortality rate of 40% showed statistically higher levels of these proteins in survivors. Patients surviving sepsis had statistically significant higher levels of apolipoprotein, albumin, LDL, transferrin and holotransferrin than individuals that succumbed, suggesting that these proteins have an inhibitory effect on LPS/LTA-induced inflammatory responses and in their absence there might be an augmented inflammatory response in sepsis. |
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Authors:
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Martha Triantafilou; Marios-Angelos Mouratis; Philipp Lepper; Rowenna Mitch Haston; Fiona Baldwin; Sarah Lowes; Mohamed Abd Elrahman Ahmed; Christian Schumann; Owen Boyd; Kathy Triantafilou |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-01 |
Journal Detail:
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Title: Virulence Volume: 3 ISSN: 2150-5608 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101531386 Medline TA: Virulence Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Cardiff University School of Medicine; Department of Child Health; University Hospital of Wales; Cardiff, UK; These authors contributed equally to this work. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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