- Paracellular transport refers to the movement of substances across epithelial or endothelial barriers by passing through the space between adjacent cells, rather than through the cells themselves.
- This intercellular route is tightly regulated by specialized structures known as tight junctions, which form a selective seal between neighboring cells at the apical region of the lateral membrane. These junctions are composed of several proteins, most notably claudins, occludin, and ZO proteins, which collectively determine the permeability and selectivity of the paracellular pathway.
- The extent and selectivity of paracellular transport vary depending on the tissue type. For example, in the small intestine and renal tubules, tight junctions allow controlled passage of ions and water, which is essential for nutrient absorption and fluid balance. In contrast, tissues like the blood-brain barrier have highly restrictive tight junctions to protect the brain from potentially harmful substances.
- Under physiological conditions, paracellular transport allows the passage of small ions, water, and certain solutes. However, during pathological states, such as inflammation or infection, tight junction integrity can be compromised. Pro-inflammatory cytokines like TNF-α and IL-1β, or bacterial virulence factors like Helicobacter pylori CagA, can disrupt tight junctions, leading to increased permeability — a phenomenon often referred to as a “leaky” barrier. This disruption is associated with various diseases, including inflammatory bowel disease, celiac disease, and gastric pathologies.
- Researchers commonly assess paracellular permeability using assays such as transepithelial electrical resistance (TEER), which measures the integrity of the cell monolayer, or by tracking the diffusion of fluorescent tracers (e.g., FITC-dextran) across the cell layer. These tools help evaluate the functional status of tight junctions and the extent of paracellular transport under different experimental or disease conditions.
