Immune function of epithelial cells
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Intercellular junctions between adjacent epithelial cells are of course required for barrier function. Intercellular junctions are located along the lateral surfaces of the epithelial cells. They are composed of the most apically oriented tight junctions, and the subjacent adherens junction and desmosome (Figure 5.2). While the latter are required for physical integrity of the epithelial monolayer, movement across tight junctions is the rate-limiting barrier for solute and particle transport. Tight junctions are physiologically dynamic and regulate the access of small solutes, water, and macromolecules into the paracellular space. Movement across tight junctions can be considered to occur via two routes, the pore pathway and the transcellular pathway. The pore pathway is a high-capacity route that is exquisitely size selective, excluding molecules with Stokes radii greater than ∼5 Å, and are also charge selective. Intestinal tight junctions allow cations to cross via the pore pathway at rates up to 10-fold greater than anions. While this cation selectivity is critical for normal physiologic function and can be reversed to anion selectivity by modifying tight junction protein expression, it is far less than that exhibited by transmembrane ion channels. Nevertheless, the paracellular channels that define the pore pathway are actively gated, i.e., they open and close, in a manner similar to transmembrane ion channels.
The cardiovascular system
C. Simon Herrington in Muir's Textbook of Pathology, 2020
The microcirculation is the capillaries, the arterioles that supply them, and the venules that drain the blood from the capillary bed. A capillary consists of a single endothelial cell encircling a lumen that only just admits the passage of red blood cells. Intercellular junctions join adjacent endothelial cells. The microcirculation is adapted to each organ and tissue. Thus, the liver sinusoids and kidney have a highly permeable fenestrated endothelium, whereas the capillaries in the brain are watertight and contribute to the blood–brain barrier. Capillary endothelial cells are surrounded by pericytes, which support them, synthesize basement membrane, and can differentiate into a variety of cell types including vascular smooth muscle cells. Capillaries act as a semipermeable membrane. They retain most of the protein but permit free exchange of fluid.
The Ultrastructure And Pathobiology Of Urinary Bladder Cancer
George T. Bryan, Samuel M. Cohen in The Pathology of Bladder Cancer, 2017
Intercellular junctions in the three lines have been described elsewhere.124,296,412 In brief, noninvasive (RBTCC-2) and invasive (RBTCC-5 and RBTCC-8) carcinoma cells have zon-ulae occludentes at the apexes of their lateral membranes (see Figure 46A). Some occludens junctions of RBTCC-5, and especially RBTCC-8 carcinoma cells, are focally attenuated, consisting of only one or two strands (see Figure 46C). Occasionally the strands are discontinuous, forming fasciae or maculae occludentes. This reproduces the appearance of occludens junctions in higher-grade invasive human transitional cell carcinomas.58,104 Focally expanded occludens junctions are observed in cultures of RBTCC-8 tumor cells (see Figure 46B). A few PF-1 gap junctions, as well as numerous desmosomes, are present in all three carcinoma cell lines.124,412 These transitional cell carcinoma lines, together with the major supporting cells of the connective tissue stroma (endothelial cells and fibroblasts) grown in vitro,384 constitute a useful biological system for the further study of the local regulation of tumor growth and tumor invasion and other problems in cancer cell biology.
Cell-cell junctions: structure and regulation in physiology and pathology
Published in Tissue Barriers, 2021
Mir S. Adil, S. Priya Narayanan, Payaningal R. Somanath
Intercellular junctions are structurally and biochemically differentiated regions of the plasma membrane through which adjacent cells interact in a specific manner. These structures were originally identified and named according to their morphology and purported function.29 To retain barrier function and to prevent the invasion of pathogens and their rapid systemic spread, cell junctions need to be kept tight and repaired quickly after vessel rupture.30 There are three functional categories of cell junction: anchoring junctions; tight, or occluding, junctions, and gap (GJ), or permeable, junctions Figure 1.17,31,32 The AJs and desmosomes provide essential adhesive and mechanical properties that contribute to barrier function but do not seal the paracellular space,33 the TJs hold cells together and form a near leakproof intercellular seal by fusion of adjacent cell membranes34 since interactions between cells are important for the assembly and maintenance of three-dimensional tissues.35 The latter is a selectively permeable barrier that generally represents the rate-limiting step of paracellular transport.33 Many cell types also possess GJs, which allow small molecules to pass from one cell to the next through channels.34
Structure–activity relationship of a peptide permeation enhancer
Published in Tissue Barriers, 2023
Drug development is often hampered by the physicochemical properties of the drug candidate. The selection of excipients may lead to an optimization of key pharmacokinetic parameters such as absorption and distribution.1 Since the majority of approved drugs are administered orally,2 sufficient intestinal absorption and resulting bioavailability is decisive for drug efficacy and safety. At epithelia, drug absorption can occur by the transcellular or paracellular pathway.3 It has been estimated that the intercellular (paracellular) space in the intestinal epithelium is about 4 Å.4 In addition, the passage of molecules through the paracellular space is regulated by networks of proteins forming different types of intercellular junctions. The most important of these connections are tight junctions (TJs),5 located at the apical side of the epithelial cells.
Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity
Published in Gut Microbes, 2021
Miguel S. Marques, Ana C. Costa, Hugo Osório, Marta L. Pinto, Sandra Relvas, Mário Dinis-Ribeiro, Fátima Carneiro, Marina Leite, Ceu Figueiredo
The most apical set of intercellular junctions are the tight junctions that act as a barrier to pathogen entry into deeper tissues. Tight junctions also control paracellular permeability across the epithelium and serve as a barrier to intramembrane diffusion of components between the apical and basolateral membrane domains.4 They are formed by various transmembrane proteins and by cytosolic proteins that connect the former to the cytoskeleton and to different types of signaling proteins.5 In epithelial cells, the transmembrane protein junctional adhesion molecule A (JAM-A), also known as F11R, has been implicated in the regulation of the barrier and in cell polarity, adhesion, migration, and invasion.6–9 The human JAM-A contains two immunoglobulin (Ig)-like loops in the extracellular domain, a single transmembrane domain, and a short 40-amino-acid cytoplasmic tail.10 The C-terminus of JAM-A contains a PDZ domain-binding motif responsible for interactions with cytoplasmic adaptors, including ZO-1/2, Afadin, and PAR3.11–14
Related Knowledge Centers
- Adherens Junction
- Cell Adhesion Molecule
- Desmosome
- Epithelium
- Gap Junction
- Paracellular Transport
- Protein Quaternary Structure
- Extracellular Matrix
- Cell
- Plasmodesma