Second messenger pathways in pulmonary host defense.
The alveolar macrophage responds to bacterial infection with the production of inflammatory mediators that include TNFalpha. Early production of TNFalpha results in increased bacterial clearance, whereas too much TNFalpha results in many of the hallmarks of bacterial sepsis. TNFalpha production is regulated at many levels, including multiple signaling pathways, that lead to transcription, translation, and release of functional TNFalpha. 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 TNFalpha in sepsis.
Monick
Martha M
MM
Department of Medicine, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City, Iowa, USA. martha-monick@uiowa.edu
Hunninghake
Gary W
GW
D000818:Animals; D006801:Humans; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D015290:Second Messenger Systems / Q000276:immunology*; D018805:Sepsis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*