Document Detail

Inflammation-induced systemic proteolysis of inter-alpha-inhibitor in plasma from patients with sepsis.
MedLine Citation:
PMID:  10695665     Owner:  NLM     Status:  MEDLINE    
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.
M Balduyck; D Albani; M Jourdain; C Mizon; A Tournoys; H Drobecq; F Fourrier; J Mizon
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2000-03-15     Completed Date:  2000-03-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375375     Medline TA:  J Lab Clin Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  188-98     Citation Subset:  AIM; IM    
Laboratoire de Biochimie, Faculté de Pharmacie, Lille, France.
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MeSH Terms
Alpha-Globulins / analysis,  metabolism*
Bacteremia / blood*
Biological Markers / blood
Critical Care
Endopeptidases / blood
Glycoproteins / blood
Inflammation / blood*
Membrane Glycoproteins*
Middle Aged
Neutrophils / enzymology
Reference Values
Sepsis / blood*,  physiopathology
Serine Proteinase Inhibitors / blood
Shock, Septic / blood*,  physiopathology
Trypsin Inhibitor, Kunitz Soybean*
Reg. No./Substance:
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

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