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Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions
Univ Hosp Ulm, Germany.
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University. (Ctr Biomat Chem)ORCID iD: 0000-0001-7888-1571
Univ Hosp Ulm, Germany.
Uppsala University.
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2018 (English)In: Seminars in Immunopathology, ISSN 1863-2297, E-ISSN 1863-2300, Vol. 40, no 1, p. 87-102Article, review/survey (Refereed) Published
Abstract [en]

Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase. This concept review article aims at identifying and describing conditions where the strict system-related control is circumvented. These include clinical settings where massive amounts of proteolytic enzymes are released from tissues, e.g., during pancreatitis or post-traumatic tissue damage, resulting in consumption of the natural substrates of the specific proteases and the available protease inhibitor. Another example of cascade system dysregulation is disseminated intravascular coagulation, with canonical activation of all cascade systems of the blood, also leading to specific substrate and protease inhibitor elimination. The present review explains basic concepts in protease biochemistry of importance to understand clinical conditions with extensive protease activation.

Place, publisher, year, edition, pages
Springer, 2018. Vol. 40, no 1, p. 87-102
Keywords [en]
Complement system, Proteases, Protease inhibitors, Trauma
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
URN: urn:nbn:se:lnu:diva-70933DOI: 10.1007/s00281-017-0646-9ISI: 000424058800008PubMedID: 28900700OAI: oai:DiVA.org:lnu-70933DiVA, id: diva2:1183113
Available from: 2018-02-15 Created: 2018-02-15 Last updated: 2018-02-15Bibliographically approved

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Nilsson Ekdahl, Kristina

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