Wrong Resemblance? Role of the Immune System in the Biocompatibility of Nanostructured Materials - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 292

these share structural characteristics of the ligand-binding domain
with MBL although they serve roles not involving the complement
system. Their major functions appear to pertain to antigen uptake
through recognition of microbial carbohydrates. However, a role as
“scavenger receptors,” i.e., receptors that serve to remove decayed
molecular species from circulation, has also been suggested [26].
One specific example is the macrophage mannose receptor (MMR).
The receptor consists of eight carbohydrate recognition domains,
however, with only two of these contributing to the ability of
recognizing carbohydrate moieties. As suggested by the name
terminal mannose residues in glycans are ligands together with
fucose and N- acetylglucosamine residues. MMR is a powerful agent
in supporting phagocytic uptake of particles with an appropriate
exposure of carbohydrates. It should be noted that lectin-mediated
particle uptake is probably not unique to phagocytic cells. This was
elegantly demonstrated by Ezekowitz et al. by simple transfection of
a mammalian cell line with no or little resemblance to mammalian
leukocytes with a construct expressing MMR [27]. At least the initial
phases of phagocytosis, i.e., internalization of yeast particles, was
completed by these cells suggesting that the ability of phagocytosis is
not exclusive to leukocytes but may rather depend on the expression
of cell surface receptors that supports the binding to such particles.
This is interesting with the broad expression of lectins since it opens
the possibility that a large number of cells this way are capable of
receptor-mediated particle uptake.
Integrins are also important in both phagocytosis and cellular
signaling [28, 29]. These receptors are heterodimers consisting
of one alpha chain and one beta chain, both with transmembrane
domains and tightly linked to the cytoskeleton. Research carried
out over the past decade strongly supports the idea that the
ligand binding by integrins is regulated by the conformation of
the receptors. In the resting, non-ligand-binding state the receptor
is kept in a bent conformation. Upon activation through cellular
stimulation, which involves rearrangements of the cytoskeleton, the
bent conformation is changed by allosteric signaling to an unbent, or
elongated, conformation that supports ligand binding. A total of 17
integrin alpha and 8 beta chains have been identified, and these form
a total of 24 known heterodimers that diff er considerably in ligand
specificity and cellular expression. The function of integrins can
largely be divided into three groups, namely (1) cell-extracellular