Biomedical Engineering Reference
In-Depth Information
includes monocytes, macrophages, dendritic cells, and neutrophil
granulocytes is capable of phagocytosis (literally meaning “eating”)
of particulate material. The same process also plays a role in the
interaction between these cells and solid materials where phagocytes
may enable restructuring or degradation of the material. Binding of
antibodies to particles greatly facilitates the uptake of these particles
by phagocytes and stimulates the production of cytokines. Following
the contact between the phagocyte and the antibody-coated particle,
receptors for the Fc part of antibodies mediate the uptake of the
particles in membrane-clad vesicles into phagocyte cytoplasm. Here,
the vesicles are fused with lipid vesicles with enzymes, typically
esterases, which may degrade not only protein species but also other
polymers. In processes where phagocytes interact with surfaces
or objects vastly larger than the cell itself, the cells show signs of
incomplete, or frustrated, phagocytosis, which releases enzymes
and oxygen radicals to the extracellular environment [18, 19]. The
enzymes may eventually aff ect the successful integration of the
nanomaterial in the body.
A third eff ector mechanism of antibody binding is comprised by
the activation of the complement system [20, 21]. The complement
system consists of approximately 30 soluble components in human
plasma and receptors expressed on the cell surface. Following antibody
binding to target surfaces, the C1 complexes bind the antibodies and
through its enzymatic components activate complement factors C2
and C4 through cleavage of these proteins into the fragments C2a
and C2b as well as C4a and C4b. The C2a and C4b fragments form an
enzyme that cleaves C3 into C3a and C3b. Since C3b together with
the b fragment of complement factor B (Bb) also is an enzyme that
may cleave C3, a positive amplification loop is established, which
rapidly covers a target surface with C3b fragments. The C3 and C4
proteins are structurally similar and both of these proteins forms
a covalent adduct with hydroxyl or amine groups on the activating
surface. The process is controlled by Factor I that inactivates the
C3bBb complex by cleavage of C3b into iC3b. Both the C3b and iC3b
fragments are facilitators of receptor-mediated phagocytosis and
appropriate receptors are expressed on all phagocytes. C3a, the
small fragment of C3 following cleavage during activation, together
with other small fragments of complement factors (usually referred
to as anaphylatoxins), is a potent mediator of inflammation, notably
with an influence on the endothelial barrier. Strong activation of the
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