VOPROSY MEDITSINSKOI KHIMII (ISSN 0042-8809)

The effect of leukocyte elastase on human plasma high molecular weight kininogen in the presence of alpha-1-proteinase inhibitor. Analysis of proteolytic degradation

   
Dotsenko V.L.1, Neshkova E.A.1, Rugnes E.2, Johansen H.2, Blokhina T. B.1, Jarovaya G.A.1

1. Russian Medical Academy for Postgraduate Education
2. School of Farmacy, Dept.Pharmacology, Oslo, Norway
PubMed Id: 11385999
Year: 2001  Volume: 47  Issue: 1  Pages: 55-71
Degranulation of polymorphonuclear leukocytes (neutrophils) and releasing of leukocyte elastase during inflammation occur not only in injured tissue but in plasma in the presence of considerable excess of alpha-1 proteinase inhibitor (alpha-1PI). However, in spite of the absence of free elastase in patients' plasma, even in such severe inflammation as peritonitis and septicaemia, degradation of the connective tissue structures and plasma proteins may be determined. However the reasons of such destructive action are not yet determined. In this paper the action of leukocyte elastase on human plasma high molecular weight kininogen (HMWK) was studied in the absence or in the presence of different concentrations of alpha-1PI. The results showed that degradation of the intact molecules of HMWK occurred under the action of elastase during 1-2 hours of combined incubation even if the concentration of alpha-1PI in the mixture in 3-5 fold exceeds the molar elastase concentration. The rate of elastase inhibition by alpha-1PI in the presence of HMWK did not depend on an order of enzyme and inhibitor addition to the incubation medium. HMWK degradation by elastase in the presence of alpha-1PI was accompanied by impairments in its adhesion function although high tolerance of HMWK inhibitory activity with respect to SH-proteinases preserved. Thus, total inhibition of leukocyte elastase by alpha-1PI, in the presence of high molecular weight kininogen develops during relatively long time interval. The pronounced destruction of intact HMWK molecules takes place during this period of gradual elastase inhibition. This fact seems to be very important in pathogenesis of thrombo-haemorrhage syndrome as a complication of severe inflammation.
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Dotsenko, V. L., Neshkova, E. A., Rugnes, E., Johansen, H., Blokhina, T. , B., Jarovaya, G. A. (2001). The effect of leukocyte elastase on human plasma high molecular weight kininogen in the presence of alpha-1-proteinase inhibitor. Analysis of proteolytic degradation. Voprosy meditsinskoi khimii, 47(1), 55-71.
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