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Is generation of C-3(H2O) necessary for activation of the alternative pathway in real life?
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala university, Sweden. (Linnaeus Ctr Biomat Chem, BMC)ORCID iD: 0000-0001-7888-1571
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. (Linnaeus Ctr Biomat Chem, BMC)
Uppsala university, Sweden.
Uppsala university, Sweden.
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2019 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 114, p. 353-361Article in journal (Refereed) Published
Abstract [en]

In the alternative pathway (AP) an amplification loop is formed, which is strictly controlled by various fluid-phase and cell-bound regulators resulting in a state of homeostasis. Generation of the "C3b-like" C3(H2O) has been described as essential for AP activation, since it conveniently explains how the initial fluid-phase AP convertase of the amplification loop is generated. Also, the AP has a status of being an unspecific pathway despite thorough regulation at different surfaces. During complement attack in pathological conditions and inflammation, large amounts of C3b are formed by the classical/lectin pathway (CP/LP) convertases. After the discovery of LP's recognition molecules and its tight interaction with the AP, it is increasingly likely that the AP acts in vivo mainly as a powerful amplification mechanism of complement activation that is triggered by previously generated C3b molecules initiated by the binding of specific recognition molecules. Also in many pathological conditions caused by a dysregulated AP amplification loop such as paroxysmal nocturnal hemoglobulinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), C3b is available due to minute LP and CP activation and/or generated by non-complement proteases. Therefore, C3(H2O) generation in vivo may be less important for AP activation during specific attack or dysregulated homeostasis, but may be an important ligand for C3 receptors in cell-cell interactions and a source of C3 for the intracellular complement reservoir.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 114, p. 353-361
Keywords [en]
Complement system, C-3(H2O), Conformation, Analysis, Proteases, Alternative pathway
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
URN: urn:nbn:se:lnu:diva-89867DOI: 10.1016/j.molimm.2019.07.032ISI: 000490625600041PubMedID: 31446306OAI: oai:DiVA.org:lnu-89867DiVA, id: diva2:1366916
Conference
17th European Meeting on Complement in Human Disease (EMCHD), 2019, Madrid, SPAIN
Available from: 2019-10-31 Created: 2019-10-31 Last updated: 2019-10-31Bibliographically approved

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Nilsson Ekdahl, KristinaMohlin, CamillaSandholm, Kerstin

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