The role of the monocyte and endothelium in mediating the host response to infection.

LPS and/or other pathogen-associated properties activate pathogen recognition receptors (or toll-like receptors) on monocytes, tissue macrophages, and endothelial cells, leading to the release of inflammatory mediators and tissue factor (with subsequent activation of coagulation). Together with products of the contact system (eg, kinins) and complement cascade (eg, C5a) (not shown), inflammatory mediators function in autocrine and paracrine loops to further activate the monocyte and local endothelium (dotted line, left, shows paracrine pathway). The various components of the coagulation cascade serve not only to activate their downstream substrate (leading to fibrin formation) but also to trigger protease-activated receptors on the surface of a variety of cell types, including the endothelium (broken line, right). The combined effects of LPS, inflammatory mediators, and serine proteases on the endothelium may result in significant phenotypic modulation (not shown). CAM indicates cell adhesion molecules; PAF, platelet activating factor; NO, nitric oxide; ROS, reactive oxygen species; MIP-2, macrophage inflammatory protein 2.