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Chapter 6: MOLECULAR AND CELLULAR BIOLOGY OF BLOOD VESSELS ENDOTHELIAL CELL-LEUKOCYTE INTERACTIONS

Endothelial cells participate actively in the development of inflammatory reactions. They are central to the recruitment of leukocytes to sites of inflammation by secreting chemotactic molecules and expressing adhesion molecules that interact with surface proteins on leukocytes.

Inflammatory cytokines increase synthesis of vasodilators by the endothelium, which causes increased blood flow to the injured area. Histamine, which is released at the site of vascular inflammation, also contracts endothelial cells in certain areas, thus increasing permeability.122 Cytokines stimulate endothelial secretion of leukocyte chemoattractant proteins (interleukin 8) and monocyte chemotactic protein 1 (MCP-1), and expression of adhesion molecules such as intercellular adhesion molecules 1 and 2 (ICAM-1 and ICAM-2), endothelial leukocyte adhesion molecule 1 (E-selectin), vascular cell adhesion molecule 1 (VCAM-1), and GMP-140, which are important regulators of leukocyte accumulation on the vascular surface.123 E-selectin and GMP-140 bind resting, but not activated, neutrophils; VCAM-1 binds to the VLA-4 antigen on monocytes and T lymphocytes; and ICAM-1 and 2 bind to the LFA-1 integrin receptor on B lymphocytes.123 The expression of these molecules appears to be differentially regulated by cytokines, thrombin, and histamine,123 so that their surface expression determines the type of leukocytes attached to the endothelial monolayer. It has been suggested that the sequential accumulation of different leukocyte classes at sites of inflammation can be explained by the differential induction of these endothelial cell adhesion molecules.124 Leukocyte adhesion molecules and chemoattractant proteins are also likely to be important in atherogenesis (see below).

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Essentials of Human Physiology

Essentials of Human Physiology

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