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Endothelial barriers: from hypothetical pores to membrane proteins
Author(s) -
Firth J. A.
Publication year - 2002
Publication title -
journal of anatomy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 118
eISSN - 1469-7580
pISSN - 0021-8782
DOI - 10.1046/j.1469-7580.2002.00047_6.x
Subject(s) - paracellular transport , tight junction , claudin , biophysics , cell junction , oncotic pressure , fluorescence recovery after photobleaching , hydrostatic pressure , adherens junction , materials science , nanopore , anatomy , chemistry , membrane , nanotechnology , biology , physics , permeability (electromagnetism) , cell , mechanics , biochemistry , cadherin , albumin
The presence of small (4–6 nm diameter) pores in nonbrain capillary walls, permeable to water and small hydrophilic solutes but not most proteins, was established 50 y ago (Pappenheimer et al. Amer. J. Physiol . 167 , 1951). This model provides a basis for long recognised features of hydraulic and oncotic pressure driven flows across capillary walls (Starling, J. Physiol . 19 , 1896). However the anatomical counterpart of the small pore system proved difficult to establish. Polarised preferences for the caveolar systems or for the paracellular pathway have now matured into a broad agreement that the main small pore pathway in continuous (nonfenestrated) capillaries is likely to be paracellular. The caveolar system is strongly associated with far rarer large pores and with opening‐up by inflammatory agents. Analogy with epithelial paracellular pathways would suggest that tight junctions are likely to be the most restrictive elements. The repeated demonstration by electron microscopy of a gap 4–5 nm wide in the tight junction strands of nonbrain endothelia failed an important test. Such a slit pore occupying the total length of the paracellular cleft would make the total pore area of capillaries in tissues such as muscle about an order of magnitude larger than physiological estimates suggested. Recognition that the tight junctions are interrupted by discontinuities much larger than small pores suggested that the tight junction might function as a shutter limiting the available cleft area rather than as the filter. Subsequent attention has focussed on other regions of the cleft and on the presence of 3 dimensional molecular meshes. Proposed sieve elements range from the glycocalyx to the adhesion molecule complexes of the adherens junctions. The molecular architecture of tight junctions and adherens junctions is moderately well defined in terms of molecular species, and there are differences at both sites between the endothelial and epithelial spectrum of protein expression. However, definition of the size‐restricting pore remains elusive and may require structural biology approaches to the spatial arrangements and interactions of the membrane molecular complexes surrounding the endothelial paracellular clefts.