the complement system #5 & #6

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Anasthesiol Intensivmed Notfallmed Schmerzther 2000 Apr;35(4):207-213

[The complement system: an old story or target of new therapeutic

approaches]?

[Article in German]

Heller A, Koch T

Klinik und Poliklinik fur Anaesthesiologie und Intensivmedizin

Universitatsklinikum Carl Gustav Carus Technische Universitat

Dresden. heller-a@...

The complement system is a multifactorial protein cascade system

which is essentially involved in the early unspecific immune

response. Its major function is the activation of cellular defense

mechanisms, opsonisation of foreign particles and the destruction of

target cells. While the impact of the different complement components

for bacterial elimination still remains controversial, overwhelming

activation of the complement cascade, however, can induce life

threatening tissue damage due to the effective cytotoxic properties.

In the last years a variety of studies demonstrated beneficial, organ

protective effects of complement modulation in models of severe

inflammation. Attempts to control the complement system include the

application of endogenous complement inhibitors e.g. C1-inhibitor (C1-

INH) or the administration of recombinant complement receptors such

as the soluble complement receptor 1 (rsCR1). Moreover antibodies

against key proteins (C3, C5), against their activation products

(C5a) or against complement receptor 3 (CR3, CD18/11b) mediated

adhesion of leukocytes to the vascular endothelium, represent

effective options of complement modulation. Besides this, insertion

of membrane bound human complement regulators (DAF- CD55, MCP- CD46

or CD59) into xenogenic donor organs has proven effectiveness to

prevent xenograft rejection. The described interventions protected

from severe organ damage in various animal models of sepsis,

myocardial and intestinal ischaemia-reperfusion injury, ARDS,

nephritis, and xenograft rejection. With respect to recent clinical

data, complement inhibition could represent a useful therapeutic

strategy to control overwhelming inflammation. Own experiments

demonstrated protective effects of complement modulation with C1 INH

and rsCR1 in a model of complement induced pulmonary injury. With

respect to sufficient host defense, however, the use of complement

inhibitors must be considered carefully.

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Immunology 2000 May;100(1):4-12

The role of complement in the acquired immune response.

Nielsen CH, Fischer EM, RG

Department of Immunology and Microbiology, University of Southern

Denmark, Odense, Denmark.

Studies over the past three decades have clearly established a

central role for complement in the promotion of a humoral immune

response. The primary function of complement, in this regard, is to

opsonize antigen or immune complexes for uptake by complement

receptor type 2 (CR2, CD21) expressed on B cells, follicular

dendritic cells (FDC) and some T cells. A variety of mechanisms

appear to be involved in complement-mediated promotion of the humoral

response. These include: enhancement of antigen (Ag) uptake and

processing by both Ag-specific and non-specific B cells for

presentation to specific T cells; the activation of a CD21/CD19

complex-mediated signalling pathway in B cells, which provides a

stimulus synergistic to that induced by antigen interaction with the

B-cell receptor (BCR); and promotion of the interaction between B

cells and FDC, where C3d-bearing immune complexes participate in

intercellular bridging. Finally, current studies suggest that CR2 may

also play a role in the determination of B-cell tolerance towards

self-antigens and thereby hold the key to the previously observed

correlation between deficiencies of the early complement components

and autoimmune disease.