microcirculation in inflammation, which is modulated and influenced by platelet–leukocyte interactions (see above) and by the coagulation system. Thrombin, the main product of the coagulation cascade, activates vascular endothelial cells, mononuclear leukocytes and platelets through the protease-activated receptors. All tissues with a microcirculation can participate in an inflammatory response. Aulus Celsus introduced four of the five cardinal symptoms of inflammation, rubor, tumor, calor, dolor, or redness, swelling, heat, and pain. All four prominently involve the microcirculation: redness and heat reflect vasodilation; dolor is caused by the stimulation of nociceptors in the inflamed tissue, which can be amplified by swelling caused by microvascular leakage. Microcirculation consists of arterioles, capillaries, and venules. Arterioles have a smooth muscle cell-containing wall and, with few exceptions, show a divergent branching pattern, meaning that blood flows from one arteriole into two branches at each bifurcation. Postcapillary venules have no smooth muscle and are instead lined by pericytes. Venules collect blood from capillaries, which start from a divergent bifurcation and end at a confluent junction. The most important function of the microcirculation during the inflammatory response is to ensure rapid and abundant delivery of leukocytes to the inflamed tissue site. Depending on the type of inflammatory stimulus, these include neutrophils, monocytes, lymphocytes, eosinophils, and basophils. Endothelial cells control the localization of the inflammatory response as well as leukocyte and plasma protein access to tissues. At sites of inflammation, endothelial cells upregulate many inflammatory adhesion molecules, cytokines, and chemokines.