Tissue responses to implanted materials - Biomaterials and Devices for the Circulatory System - page 7

important component of innate immunity and involves cells such as neu-
trophils, macrophages and natural killer (NK) cells. As mentioned previ-
ously, neutrophils and macrophages destroy material that is recognised as
being foreign through the use of reactive oxygen intermediates and prote-
ases. However, the release of such powerful and destructive molecules can
result in damage to local native tissue. Also, macrophages release several
factors that have local and systemic effects, such as tumour necrosis factor,
IL-12, coagulation factors, angiogenic factors, fi broblast activating factors,
transforming growth factor- β and matrix metalloproteinases (Mitchell,

2004).
An important component of the innate immune system that needs to be
considered in more detail, particularly in its role in bioprosthetic device
implantation, is the complement system . Complement is a system of pro-
teins that becomes activated at an early stage of the infl ammatory response,
although the exact role of complement in this process is not completely
understood. Activation of the complement system is an early-acting mecha-
nism that triggers and amplifi es the acute infl ammatory response. In inac-
tive form, the complement system consists of nine components numbered
C1 to C9, while in its activated state the system presents over 20 cleavage
products. The complement system operates via three pathways (Fig. 1.2).
The 'classic pathway' of complement activation is triggered by binding of
antibody-antigen complexes to C1, eventually resulting in cleavage of C3
and C5 with production of C3b and C5b and of the anaphylatoxins C3a and
C5a. Anaphylatoxins may promote characteristic phenomena in acute
infl ammatory injury such as vasodilatation with increased vascular perme-
ability, leucocyte activation, chemotaxis and adhesion, and phagocytosis of
microorganisms by neutrophils and monocytes. The 'alternative pathway'
does not require activation by an antibody and is spontaneously initiated
by the hydrolysis of C3. This results in the continuous production of C3b in
a process known as C3 tickover. The 'lectin pathway' involves activation of
complement by lectins such as mannan biding lectin (MBL) and MBL-
associated serine proteases (MASPs). The chemotactic effects of the com-
plement component C3a and the ability of C3a and C5b-9 (also known as
membrane attack complex or MAC) to activate leucocytes and endothelial
cells (Hansch et al. , 1987; Gerard and Gerard, 1994) are important factors
leading to infl ammatory tissue injury. MAC causes lysis of prokaryotic cells
but also activates endothelium and leucocytes (Cotran et al. , 1994; Moore,
1994). Many studies have demonstrated that both the classic and the alter-
nate complement pathways (possibly through contact with foreign mate-
rial) undergo activation during cardiac surgery (Howard et al. , 1988;
Tennenberg et al. , 1990; Bruins et al. , 2000; Diegeler et al. , 2000; Olsson
et al. , 2000; Holmes et al. , 2002). Furthermore, there is an association
between complement and myocardial ischaemic/reperfusion injury

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