Microvascular Permeability and Tumor Metastasis - Bioanalysis Advanced Materials Methods and Devices - page 50

indirect evidence indicates that there are junctional strands with discontinuous
leakages [ 13 ] and fiber matrix components [ 57 , 72 ] at the endothelial surface
(Fig. 4.1b ). It has been concluded that the transport of proteins or other
macromolecules is through vesicle shuttle mechanisms [ 65 ]. In disease, large
gaps are formed in the microvessel endothelium to allow the passage of plasma
proteins and cells such as blood cells and tumor cells. Microvascular permeability is
a quantitative measure of how permeable the microvessel wall is to all kinds of
substances including water and solutes with a variety of sizes. Under healthy
conditions, the microvessel wall maintains a normal permeability to water and
small solutes for the material exchange during our body's metabolic processes.
By contrast, in disease, the integrity of the vessel wall structure can be destroyed
and much larger particles such as proteins, leukocytes, and tumor cells can transfer
through the wall. It is the effect of transvascular pathways at the vessel wall and their
structural barriers that determines and regulates the microvascular permeability.
Therefore, we first introduce basic information about transport across microvessels.
4.2 Microvascular Permeability and Transport
Across Microvessels
The endothelial cells lining the microvessel walls provide the rate-limiting barrier
to extravasation of plasma components of all sizes from electrolytes to proteins.
To date, four primary pathways have been observed in the wall of a microvessel by
using electron microscopy: intercellular clefts, transcellular pores, vesicles, and
fenestra (Fig. 4.2 ). Microvessels of different types and in different tissues may have
different primary transvascular pathways. Under different physiological and patho-
logical conditions, the primary pathway can be changed for the same microvessel
(summarized in [ 57 ]).
Interendothelial (Intercellular) Cleft . The cleft between adjacent endothelial cells
is widely believed to be the principal pathway for water and hydrophilic solute
transport through the microvessel wall under normal physiological conditions. The
interendothelial cleft is also suggested to be the pathway for the transport of high
molecular weight plasma proteins, leukocytes, and tumor cells across microvessel
Fig. 4.2 Schematic depiction of various transvascular pathways in the microvessel wall