| Inflammation-induced systemic proteolysis of inter-alpha-inhibitor in plasma from patients with sepsis. | |
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MedLine Citation:
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PMID: 10695665 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inter-alpha-inhibitor (IalphaI) is a human plasma serine proteinase inhibitor. It contains one light peptide chain called bikunin that exerts antiproteinase activity and other antiinflammatory functions. Bikunin is covalently linked to two heavy chains that, after tissular diffusion, stabilize the extracellular matrix. Owing to its negative acute-phase reactant character and its susceptibility to proteolysis, IalphaI has been implicated in the pathophysiology of sepsis. Moreover, IalphaI has been shown to exert a protective effect on a pig model of endotoxic shock. Twenty patients admitted to the intensive care unit (ICU) for a septic syndrome were included in the present study. IalphaI and antithrombin III (ATIII) levels were measured on admission. Sequential measurements of IalphaI could be done in 4 patients. We demonstrate that IalphaI levels are significantly decreased in plasma samples collected on admission from patients with sepsis (59 +/- 32 mg/L vs 241 +/- 70 mg/L; P < .0001). This decrease was greater in severe sepsis and septic shock than in sepsis. Death was not predictable from initiol IalphaI levels. In 2 patients with a favorable course, IalphaI values regularly increased during the ICU stay. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot analysis and microsequencing, we characterized IalphaI-related components in plasma from several patients; they obviously arise from IalphaI through proteolytic cleavage. Thus, systemic proteolysis and decreased biosynthesis both contribute to the fall in the plasma level of IalphaI. Because IalphaI is very sensitive to proteolysis by polymorphonuclear granulocytes (PMNs) that are stimulated during sepsis, we suggest that IalphaI plasma level would be a useful marker for neutrophil proteinase activity. ATIII, as well as IalphaI, is considered a negative acute phase protein. Because in vitro ATIII is less susceptible than IalphaI to proteolysis by PMNs and because their relative levels weakly correlated, we suggest that an unspecific systemic proteolysis is not significantly involved in the ATIII deficiency occurring in sepsis. |
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Authors:
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M Balduyck; D Albani; M Jourdain; C Mizon; A Tournoys; H Drobecq; F Fourrier; J Mizon |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of laboratory and clinical medicine Volume: 135 ISSN: 0022-2143 ISO Abbreviation: J. Lab. Clin. Med. Publication Date: 2000 Feb |
Date Detail:
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Created Date: 2000-03-15 Completed Date: 2000-03-15 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375375 Medline TA: J Lab Clin Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 188-98 Citation Subset: AIM; IM |
Affiliation:
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Laboratoire de Biochimie, Faculté de Pharmacie, Lille, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Alpha-Globulins / analysis, metabolism* Bacteremia / blood* Biological Markers / blood Critical Care Endopeptidases / blood Female Glycoproteins / blood Humans Inflammation / blood* Male Membrane Glycoproteins* Middle Aged Neutrophils / enzymology Reference Values Sepsis / blood*, physiopathology Serine Proteinase Inhibitors / blood Shock, Septic / blood*, physiopathology Trypsin Inhibitor, Kunitz Soybean* |
| Chemical | |
Reg. No./Substance:
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0/Alpha-Globulins; 0/Biological Markers; 0/Glycoproteins; 0/Membrane Glycoproteins; 0/SPINT2 protein, human; 0/Serine Proteinase Inhibitors; 39346-44-6/inter-alpha-inhibitor; 9088-41-9/Trypsin Inhibitor, Kunitz Soybean; EC 3.4.-/Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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