Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schaefer, U; Brücker, B; Elbers, A; Neugebauer, E.
The capacity of alpha2-macroglobulin to inhibit an exogenous protease is significantly increased in critically ill and septic patients.
Shock. 2004; 22(1):16-22
Doi: 10.1097/01.shk.0000130586.63862.27
Web of Science
PubMed
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- Abstract:
- The image of alpha2-macroglobulin is based on a paradigm evolved in the 1970s. During this decade alpha2-macroglobulin was shown to irreversibly entrap and thereby inhibit a maximum of two proteases. Additional binding of nonproteolytic proteins, i.e., inflammatory mediators and growth factors, is dependent on the conformational status of alpha2-macroglobulin. It was our aim to clarify whether the interaction of nonproteolytic proteins with alpha2-macroglobulin during inflammatory conditions might also modulate the capacity of alpha2-macroglobulin to inhibit proteases. To explore this possibility, bromelain, an exogenous protease, was titrated against plasma of critically ill or septic patients, whose pathophysiological conditions are defined by a massive release of inflammatory mediators. The stoichiometry of bromelain inhibition by alpha2-macroglobulin was quantified by caseolytic activity assays. The maximal alpha2-macroglobulin/bromelain inhibition ratios were significantly increased (1:6 and 1:8 in the two patient groups, P < 0.01) as compared with control groups (1:2 with purified alpha2-macroglobulin and 1:4 in healthy volunteers). The increase of alpha2-macroglobulin inhibition capacity in patients was paralleled by the appearance of a large signal on Western blots, suggesting the formation of additional complexes. Our results demonstrate alpha2-macroglobulin to have more flexibility than had been thought, and it may thereby contribute to a shift in a 30-year-old paradigm.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Bromelains - pharmacology
- Critical Illness - pharmacology
- Female - pharmacology
- Humans - pharmacology
- Male - pharmacology
- Middle Aged - pharmacology
- Protease Inhibitors - pharmacology
- Reference Values - pharmacology
- Sepsis - physiopathology
- alpha-Macroglobulins - metabolism
- Find related publications in this database (Keywords)
- protease inhibitor
- bromelain
- inhibitory capacity
- inflammation