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- Title
Urinary Bikunin Determination Provides Insight into Proteinase/ Proteinase Inhibitor Imbalance in Patients with Inflammatory Diseases.
- Authors
Mizon, Charlotte; Piva, Frank; Queyrel, Viviane; Balduyck, Malika; Hachulla, Eric; Mizon, Jacques
- Abstract
Bikunin (BK) is a Künitz-type proteinase inhibitor responsible for most of the antitryptic activity of urine and so is known as the urinary trypsin inhibitor. As its excretion increases in inflammatory conditions, it is often considered to be a positive acute phase protein (APP). However, the gene for BK is downregulated in inflammation. In human plasma the major part of BK is covalently linked through a glycosaminoglycan chain to one or two homologous peptide heavy chains, thus forming high molecular weight proteinase inhibitors called pre-α-inhibitor (PαI) and inter-α-inhibitor (IαI), respectively. The C-terminal parts of these heavy chains are very sensitive to proteolysis. Neutrophil proteinases in particular are able to release from IαI and PαI BK (Mr about 25000) which retains its antitryptic activity and is quickly excreted in urine. It was therefore an early supposition that the higher urinary excretion of BK occurring during inflammatory diseases should be, at least in some respect, related to a partial proteolysis of IαI and PαI. In this study we observed that BK, determined as antitryptic activity, was clearly increased in urine from 35 patients with inflammatory diseases varying in origin and severity (76.5±75.5 IU/g vs. reference value <10 IU/g creatinine). This increase seems mainly to be associated with polymorphonuclear leukocyte activation, monitored by human leukocyte elastase (HLE) determination rather than with the acute phase response assessed by C-reactive protein (CRP) measurement. For all the patients we found that the urinary levels of BK and serum concentration of intact IαI correlated inversely (r=-0.36; p=0.03), in agreement with the presumed precursorproduct relationship linking IαI and BK. We also proved that urinary BK was significantly higher, and serum IαI was significantly lower, in samples with plasma HLE values above the reference: 90 µg/l. Taken together, our results demonstrate that BK, the urinary excretion of which is increased in inflammatory conditions, originates, at least partly, from IαI and PαI by proteolytic cleavage. Consequently, urinary BK determination provides information on the severity of systemic proteolysis occurring in inflammation. We also demonstrated that during inflammatory diseases IαI and PαI concentrations in serum are dependent on their increased utilization as well as on the regulation of their biosynthesis.
- Publication
Clinical Chemistry & Laboratory Medicine, 2002, Vol 40, Issue 6, p579
- ISSN
1434-6621
- Publication type
Article