IFISE   05411
INSTITUTO DE FISIOLOGIA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Complement activation and disease: protective effects of hyperbilirubinemia
Autor/es:
BASIGLIO, C.; ARRIAGA, SANDRA M.; PELUSA, F.; ALMARA, ADRIANA M; KAPITULNIK, J; MOTTINO, ALDO D
Revista:
CLINICAL SCIENCE (LONDON, ENGLAND : 1979)
Editorial:
PORTLAND PRESS LTD
Referencias:
Año: 2010 vol. 118 p. 99 - 113
ISSN:
0143-5221
Resumen:
Complement, an important effector mechanism of the immune system, is an enzymatic cascade
of approx. 30 serum proteins leading to the amplification of a specific humoral response. It can
be activated through the classical or alternative pathways, or through the mannose-binding lectin
pathway. The activation of the classical pathway is initiated by the binding of the C1 component
to antigen-bound antibodies, known as immunocomplexes. C1 is a complex of one molecule of
C1q, two molecules of C1r and two molecules of C1s. C1q contains three copies of a Y-shaped
fundamental unit with globular heads included in its structure, which play a major role in the
interaction with the Fc portion of immunoglobulins. Deficient or exacerbated activation of
the complement system leads to diseases of variable severity, and pharmacological inhibition of the
complement system is considered as a therapeutic strategy to ameliorate the inflammatory effects
of exacerbated complement activation. Bilirubin is a product of haem degradation by the concerted
action of haem oxygenase, which converts haem into biliverdin, and biliverdin reductase, which
reduces biliverdin to UCB (unconjugated bilirubin). UCB exerts both cytoprotective and cytotoxic
effects in a variety of tissues and cells, acting either as an antioxidant at low concentrations or
as an oxidant at high concentrations. In the present review, we describe in detail the anticomplement
properties of bilirubin, occurring at levels above the UCB concentrations found in
normal human serum, as a beneficial effect of potential clinical relevance. We provide evidence
that UCB interferes with the interaction between C1q and immunoglobulins, thus inhibiting the
initial step in the activation of complement through the classical pathway. A molecular model is
proposed for the interaction between UCB and C1q.