Biomedical Engineering Reference
In-Depth Information
9.5.12
Blood Group Antigens
α
(1,2)-Fucosyltransferase Fut1 adds the terminal fucose to form blood group
antigen glycan Lewis-Y (CD174) and its precursor glycan H2 (CD173) that are
predominantly expressed on erythrocytes and subsets of vascular endothelial cells.
Bone marrow and microvascular endothelial cells (but not macrovascular endothe-
lial cells, such as aortic endothelial cells) stimulated by tumor-necrosis factor-
α
increase their production of blood group glycans-H2 and Lewis-Y. Fucosylated
blood group glycans-H2 and Lewis-Y promote tumor angiogenesis [ 937 ]. Factors
of malignant cells such as TNF
elicit endothelial cell migration to form new blood
vessels. Glycans-H2 and Lewis-Y are concentrated on pseudopodial extensions of
endothelial cells.
α
9.6
Transendothelial Mass Transfer
Vascular endothelium is a selective permeable barrier that regulates the transfer of
molecules and cells from blood to underlying tissues. Transport across the endothe-
lium depends on relative intramural pressure and concentration gradients. Molecule
transport across endothelium is influenced by molecule characteristics: molecular
size, charge, shape, and carbohydrate content. In fact, transport properties of the
endothelial barrier are sensitive to both its chemical and mechanical environment.
Transport across the endothelium use intra- and paracellular routes. Intracellular
route corresponds to vesicular transcytosis. Paracellular route is enabled by breaks
in tight (size
20 nm) and adherens junctions as well as interendothelial leaky cleft
uncovered by the glycocalyx (size 80-1330 nm at cell division sites and 15-1000 nm
in dying or dead cell zones [ 938 ]). Intercellular cleft can be strongly sealed by
tight junctions. Mechanical cohesion of the endothelial monolayer is supported by
adherens junctions. Adherens junction connects the actin cytoskeleton to the plasma
membrane.
Endothelial permeability varies according to the state of the cytoskeleton, i.e.,
to the width of intercellular spaces that narrows or enlarges with endothelial cell
relaxation or contraction.
Flowing blood shears the wetted (luminal) surface of endothelial cells endowed
with a glycocalyx that yields the first barrier to transport of solutes and water
between blood and tissue, hence modulating the permeability to solutes. Mechanical
forces influence transendothelial molecular flux via both intra- and paracellular
routes.
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