The recruitment of leukocytes from the blood stream to extravascular sites of inflammation is necessary for an effective inflammatory response. The recruitment is mediated by #Cell #Adhesion #Molecules, cytokines and chemoattractants which together coordinate this complex series of events. The adhesion cascade involves five steps which occur in sequence but may overlap in time. At sites of inflammation in the systemic circulation (as opposed to the pulmonary circulation), post-capillary venule endothelium becomes activated by the local generation of a variety of inflammatory mediators. Histamine, thrombin and LTC4 lead to a rapid expression of P-selectin on the endothelial surface while the early proinflammatory cytokines such as IL-1 and TNFα lead to de novo synthesis of both P- and E-selectin as well as ICAM-1 and VCAM-1 resulting in increased surface expression at time points greater than 2 hours following stimulation. When endothelium is exposed to these cytokines especially in the presence of FN for prolonged periods (as during chronic infection), the volume of the endothelial cell expands and it becomes columnar, similar to the morphology in high endothelial venules in lymph nodes.
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