Cellular Barriers after Extravasation: Leukocyte Interactions with Polarized Epithelia in the Inflamed Tissue

Figure 1

Endothelial and epithelial barriers determine the different stages of leukocyte migration in its journey towards the inflammatory focus in complex tissues. The parenchymal three-dimensional organization contributes to establish an haptotactic and chemotactic gradient (1) Leukocyte adhesion and transendothelial migration or diapedesis. (2) Exiting the vessel. Once they reach the subendothelial space, leukocytes traverse the basement membrane and interact with pericytes, which promote the complete extravasation of immune cells via adhesion receptors. (3) Interstitial migration. Leukocytes switch from a two-dimensional to a less adhesive three-dimensional migration to circumvent topological constraints in the stromal barrier. Fibroblasts help leukocyte navigation by maintaining protein scaffolds and secreting mediators such as cytokines and growth factors, which act as chemotactic cues. (4) Interaction with polarized epithelial barriers. Following haptotactic and chemotactic gradients, leukocytes encounter polarized epithelial cells and often undergo transepithelial migration. The polarized distribution of the adhesive and chemotactic machineries mediates leukocyte guidance through the parenchymal epithelia for immunosurveillance or the clearance of pathogens and dysfunctional cells.