Fig. 12.1.

Depiction of neutrophil responses during intestinal inflammation in response to Salmonella infection. Salmonellae infect epithelial cells, stimulating the production of chemokines (interleukin-8 [IL-8]), cytokines (IL-1β and tumor necrosis factor-α [TNF-α]), and other proinflammatory mediators. Endothelial cells stimulated by inflammatory mediators produce chemoattractants (such as IL-8) and display adhesion molecules that promote neutrophil emigration. The three steps of neutrophil (polymorphonuclear [PMN]) emigration capture/rolling (mediated by selectins), adhesion (mediated by β₂ integrins), and transendothelial migration (mediated by integrins and platelet/endothelial cellular adhesion molecule) occur on activated endothelium. Chemoattractant molecules such as IL-8 trigger neutrophil emigration. In inflamed tissues cytokines (IL-1β and TNF-α) and a variety of other proinflammatory mediators stimulate the neutrophil oxidase complex to produce reactive oxygen intermediates (ROIs; O₂⁻ and H₂O₂ and their derivatives). Activated neutrophils degranulate to release proteases and other hydrolases, cationic peptides (defensins), myeloperoxidase, and other products into the tissue. Activated neutrophils synthesize a variety of inflammatory mediators, including prostaglandins (PGE₂) that modulate the inflammatory response. The products of activated neutrophils (ROIs, proteases, and mediators) stimulate epithelial secretion and alter tight junction permeability, promoting diarrhea. Neutrophils eventually migrate across the infected epithelium by a mechanism that involves integrins, disrupting tight junction integrity and increasing permeability to bacterial products, thus exacerbating the inflammatory response.