Heinen, Dennis

[["dc.bibliographiccitation.firstpage","251"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","HISTOLOGY AND HISTOPATHOLOGY"],["dc.bibliographiccitation.lastpage","258"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Jozsi, M."],["dc.contributor.author","Manuelian, T."],["dc.contributor.author","Heinen, S."],["dc.contributor.author","Oppermann, Martin"],["dc.contributor.author","Zipfel, Peter F."],["dc.date.accessioned","2018-11-07T10:52:37Z"],["dc.date.available","2018-11-07T10:52:37Z"],["dc.date.issued","2004"],["dc.description.abstract","Complement is a central element of innate immunity and this vital defense system initiates and coordinates immediate immune reactions which attack and eliminate microbes, foreign particles and altered self cells. Newly generated activation products are extremely toxic and consequently, activation is highly restricted in terms of time and space. The initial activation of the alternative complement pathway occurs continuously and the early phase acts indiscriminatoryl and forms on any surface. However, the system discriminates between self and foreign, and therefore allows activation on foreign surfaces e.g. Microbes, and restricts activation on host cells. Consequently, self cells and tissues are protected from the harmful activation products. This protection is mediated by specific regulators or inhibitors, which exist in the fluid phase and/or in membrane-bound forms. Here we review a novel mechanism, i.e. the attachment of the soluble complement regulator factor H to the surface of self cells. This attachment, which is demonstrated experimentally by means of immunofluorescense microscopy and by flow cytometry, increases the inhibitory potential at the cell surface and mediates protection by reducing the local formation of toxic inflammatory products. This attachment is highly relevant and has pathophysiological consequences in several human diseases, including Factor H-associated hemolytic uremic syndrome (FH-HUS), membrano-proliferative glomerulonephritis type II, recurrent microbial infections and chronic inflammation, e.g. rheumatoid arthritis and immune evasion of tumor cells. Defects of this safeguard activity have been recently understood in patients with FH-HUS. Point mutations in the Factor H gene occurring in the C-terminus of the protein result in impaired cell binding capacity of Factor H and, consequently, during an inflammatory insult endothelial cells are not properly protected and are damaged."],["dc.identifier.isi","000188355400030"],["dc.identifier.pmid","14702193"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49151"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","F Hernandez"],["dc.relation.issn","0213-3911"],["dc.title","Attachment of the soluble complement regulator factor H to cell and tissue surfaces: relevance for pathology"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","342"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Clinical & Experimental Immunology"],["dc.bibliographiccitation.lastpage","352"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Oppermann, Martin"],["dc.contributor.author","Manuelian, T."],["dc.contributor.author","Jozsi, M."],["dc.contributor.author","Brandt, E."],["dc.contributor.author","Jokiranta, T. S."],["dc.contributor.author","Heinen, S."],["dc.contributor.author","Meri, S."],["dc.contributor.author","Skerka, C."],["dc.contributor.author","Gotze, O."],["dc.contributor.author","Zipfel, Peter F."],["dc.date.accessioned","2018-11-07T09:51:20Z"],["dc.date.available","2018-11-07T09:51:20Z"],["dc.date.issued","2006"],["dc.description.abstract","The complement inhibitor Factor H has three distinct binding sites for C3b and for heparin, but in solution uses specifically the most C-terminal domain, i.e. short consensus repeats (SCR) 20 for ligand interaction. Two novel monoclonal antibodies (mABs C14 and C18) that bind to the most C-terminal domain SCR 20 completely blocked interaction of Factor H with the ligands C3b, C3d, heparin and binding to endothelial cells. In contrast, several mAbs that bind to the N-terminus and to the middle regions of the molecule showed no or minor inhibitory effects when assayed by enzyme-linked immunosorbent assay (ELISA) and ligand interaction assays. This paradox between a single functional binding site identified for native Factor H versus multiple interaction sites reported for deletion constructs is explained by a compact conformation of the fluid phase protein with one accessible binding site. On zymosan particles mAbs C14 and C18 blocked alternative pathway activation completely. Thus demonstrating that native Factor H makes the first and initial contact with the C terminus, which is followed by N terminally mediated complement regulation. These results are explained by a conformational hypothetical model: the native Factor H protein has a compact structure and only one binding site accessible. Upon the first contact the protein unfolds and exposes the additional binding sites. This model does explain how Factor H mediates recognition functions during complement control and the clustering of disease associated mutations in patients with haemolytic uraemic syndrome that have been reported in the C-terminal recognition domain of Factor H."],["dc.identifier.doi","10.1111/j.1365-2249.2006.03071.x"],["dc.identifier.isi","000236766600021"],["dc.identifier.pmid","16634809"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35890"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0009-9104"],["dc.title","The C-terminus of complement regulator Factor H mediates target recognition: evidence for a compact conformation of the native protein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]