Diapedesis

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Diapedesis is the movement of leukocytes across the endothelial lining of blood vessels to interstitial fluid (IF). The process is driven by chemotactic factors which serve to upregulate expression of adhesion molecules on the endothelial cells of postcapillary venules adjacent to the site of infection. Neutrophils, monocytes and NK cells use "roll-to-stop" kinetics in order to slow down and "ooze through" (diapedesis) interendothelial spaces between endothelial cells and infiltrate the infected tissue.

Upon recognition of and activation by pathogens, resident macrophages in the infected tissue release cytokines such as IL-1, TNF and chemokines. IL-1 and TNF cause the endothelial cells of blood vessels close to the site of infection to express adhesion molecules such as integrin receptors and selectin. Like velcro, selectin ligands on the leukocyte bind selectin molecules on the inner wall of the vessel with marginal affinity to slow the leukocyte down near the infected tissue. This causes the leukocyte to slow down and begin rolling on the inner surface of the vessel wall. At the same time, chemokines released by macrophages activate the rolling leukocytes and cause their integrin molecules to switch from the default low-affinity state to a high-affinity state in which they can bind tightly to complementary integrin receptors that have been expressed on the endothelial cells. At this point, the integrin (VLA-4, LFA-1 or Mac-1) on the surface of the leukocytes is now able to produce the "stopping" effect by binding the integrin receptors (VCAM-1 or ICAM-1) on the inner wall of the vessel with high affinity. This leads to immobilization of leukocytes and the reorganization of their cytoskeletons in such a way that they are 'spread' out over the endothelial cells. In this form, they are thus able to pass between gaps in the vessel's endothelial cells, a process known as diapedesis.

Diapedesis usually happens when an area is injured or damaged and an inflammatory response is needed. This trafficking system is regulated by the background cytokine environment produced by the inflammatory response. In Leukocyte Adhesion Deficiency (LAD) there is defective integrin which impairs the ability of the leukocytes to stop and undergo diapedesis. Neutrophilia is a hallmark of LAD.