Animation of the Mechanism for Early Inflammation and Diapedesis (Extravasation)
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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) During the very early stages of inflammation, stimuli such as injury
or infection trigger the release of a variety of mediators of inflammation such as leukotrienes, prostaglandins, and histamine. The binding of these mediators to their receptors on endothelial cells leads to
vasodilation, contraction of endothelial cells, and increased blood
vessel permeability. In addition, the basement membrane surrounding the capillaries becoming rearranged so as to promote the migration of leukocytes and the movement of plasma macromolecules from the capillaries into the surrounding tissue.
2) The binding of histamine to histamine receptors on endothelial cells triggers an upregulation of P-selectin molecules and platelet-activating factor (PAF) on the endothelial cells that line the venules.
3). The P-selectins then are able to reversibly bind to corresponding P-selectin glycoprotein ligands (PSGL-1) on leukocytes. This reversible binding enables the leukocyte to now roll along the inner wall of the venule.
4) The binding of PAF to its corresponding receptor PAF-R on the leukocyte upregulates the surface expression of leukocyte function-associated molecule-1 (LFA-1) on the surface of the leukocyte.
5) The LFA-1 molecules on the rolling leukocytes can now bind firmly to intercellular adhesion molecule-1 (ICAM-1) found on the surface of the endothelial cells forming the inner wall of the blood vessel.
6) The leukocytes flatten out, squeeze between the constricted endothelial cells, and move across the basement membrane as they are are attracted towards chemotactic agents such as the complement protein C5a and leukotriene B4 generated by cells at the site of infection or injury.