ref Robbins 8/e p45,9/ep74 Several mechanisms may contribute to increased vascu- lar permeability in acute inflammatory reactions: * Endothelial cell contraction leading to intercellular gaps in postcapillary venules is the most common cause of increased vascular permeability. Endothelial cell con- traction occurs rapidly after binding of histamine, bra- dykinin, leukotrienes, and many other mediators to specific receptors, and is usually sho-lived (15 to 30 minutes). A slower and more prolonged retraction of endothelial cells, resulting from changes in the cytoskel- eton, may be induced by cytokines such as tumor necro- sis factor (TNF) and interleukin-1 (IL-1). This reaction may take 4 to 6 hours to develop after the initial trigger and persist for 24 hours or more. * Endothelial injury results in vascular leakage by causing endothelial cell necrosis and detachment. Endothelial cells are damaged after severe injury such as with burns and some infections. In most cases, leakage begins immediately after the injury and persists for several hours (or days) until the damaged vessels are throm- bosed or repaired. Venules, capillaries, and aerioles can all be affected, depending on the site of the injury. Direct injury to endothelial cells may also induce a delayed prolonged leakage that begins after a delay of 2 to 12 hours, lasts for several hours or even days, and involves venules and capillaries. Examples are mild to moderate thermal injury, ceain bacterial toxins, and x- or ultraviolet irradiation (i.e., the sunburn that has spoiled many an evening after a day in the sun). Endo- thelial cells may also be damaged as a consequence of leukocyte accumulation along the vessel wall. Activated leukocytes release many toxic mediators, discussed later, that may cause endothelial injury or detachment.