Animation of the Mechanism for Late Inflammation and Diapedesis (Extravasation)
Most leukocyte diapedesis (extravasation) occurs in post-capillary venules because hemodynamic shear forces are lower in these venules. This makes it easier for leukocytes to attach to the inner wall of the vessel and squeeze out between the endothelial cells.
1) Usually within two to four hours of the early stages of inflammation, tissue macrophages activated by local injury or infection release proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1).
2) The binding of TNF and IL-1 to receptors on endothelial cells triggers an maintains the inflammatory response by upregulation the production of E-selectin molecules and maintaining P-selectin expression on the endothelial cells that line the venules.
3). The E-selectins on the inner surface of the endothelial cells can now bind firmly to corresponding E-selectin ligand-1 (ESL-1) on leukocytes.
4) The leukocytes flatten out, squeeze between the constricted endothelial cells, and move across the basement membrane as they are are attracted towards chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) generated by cells at the site of infection or injury.