PAMPs Induce PRRs to Release Cytokines That Attract Leukocytes

PAMPs Induce PRRs to Release Cytokines That Attract Leukocytes 

IL-1 is stable, and it diffuses to and activates receptors (IL-1 receptors) on adjacent and distant cells. The IL-1 receptor of endothelial cells is especially important (Fig. 13.5a). In all cells, the IL-1 ligand bound to its receptor causes surface expression of a second cytokine, tumor necrosis factor-a (TNF-a). TNF-a was originally described as a factor that kills (causes necrosis of) mouse fibrosarcoma (cancer) cells but not normal mouse fibroblasts. TNF-a is released from the cell surface by an adamalysin protease, TNF alpha converting enzyme (TACE). TACE is also known as ADAM 17, one of more than 40 cell surface bound adamalysins related to the ADAM-TS2 subfamily (Sect. 8.2.1). Unlike IL-1, TNF-a is unstable and can only activate TNF receptors on nearby cells. It usually produces responses that supplement those from IL-1 activation (Fig. 13.5b). 

Neutrophil Endothelial Adhesion, Emigration of Neutrophils, Activation of Neutrophils, Plasminogen activator 

Ligand-bound IL-1 and TNF receptors activate intracellular protein kinases called mitogen-activated protein (MAP) kinases. These kinases phosphorylate serine or threonine residues on adjacent proteins in response to extracellular stimuli that were first identified as mitogenic because they induced fibroblast growth factors (Sect. 13.2.5). IL-1 or 

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