Second Messenger Pathways in Pulmonary Host Defense

The alveolar macrophage responds to bacterial infection with the production of inflammatory mediators that include TNFα. Early production of TNFα results in increased bacterial clearance, whereas too much TNFα results in many of the hallmarks of bacterial sepsis. TNFα production is regulated at many levels, including multiple signaling pathways, that lead to transcription, translation, and release of functional TNFα. Interactions of mitogen-activated protein (MAP) kinases, lipid signaling pathways, and oxidant-mediated mechanisms regulate the response of alveolar macrophages to infection. Animal models of sepsis support the central role played by macrophage-derived TNFα in sepsis.