Publication: Attachment of the soluble complement regulator factor H to cell and tissue surfaces: relevance for pathology
Authors
Józsi, M. ; Manuelian, T. ; Heinen, S. ; Oppermann, M. ; Zipfel, P.F.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
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), membranoproliferative
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.
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