Biomedical Engineering Reference
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complement system may consequently cause a breakdown in the
function of vascular system leading to a rapid and life-threatening
drop in blood pressure (shock) and disseminated intravascular
coagulation.
While the above-mentioned activation pathway with antibody as
the initiating event is referred to as the “classical” pathway, other
antibody independent pathways of complement activation also
exist. These include the “alternative pathway” where a spontaneous
deposition of autoactivated C3 on surfaces catalyzes further
deposition of C3b through formation of the C3bBb convertase.
On host cell, such deposition is avoided by cell surface-expressed
molecules that catalyzes the proteolytic degradation of C3. During the
past 20 years of research, it has become evident that certain lectins,
i.e., carbohydrate-binding proteins that are not antibodies, also may
contribute to the activation of the complement system through the
“lectin pathway” in plasma [22]. Mannan-binding lectin (MBL) binds
glycans with terminal mannose,
N-
acetylglucose, or glucose residues.
These are typically exposed on the surfaces of viruses, bacteria, and
fungi and the opsonization of these microorganisms via complement
deposition is clearly important to avoid infections. MBL mediates
complement deposition through the associated MBL-associated
serine proteases (MASP), notably through the activation of C4 and
C2 by MASP-2. More recently, the group of ficolins has also attracted
attention [23]. While ficolins also associate with MASP-2, their
ligands are not primarily carbohydrates but acetylated compounds,
including acetylated sugars, e.g.,
N-
acetylglucosamine.
10.2.3 Cell-BoundReceptors
In addition to the soluble factors mentioned above, a large number
of receptors expressed on the cell surface of leukocytes are also
relevant in the immune response to nanomaterials. Several of these
are involved in uptake of particulate material. These receptors can
be classified as mainly part of the innate immune system. Unlike the
genes encoding antibodies, the proteins are encoded by germ-line
genes that are not subject to any somatic recombination or mutation.
The ligand-binding potential of these receptors is unaltered
throughout life and is conserved in the human population.
On the surface of several phagocytes, notably macrophages
and dendritic cells, several lectins are expressed [24, 25]. Many of
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