Daniel R. Meldrum, MD, Brian D

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Presentation transcript:

Nitric oxide downregulates lung macrophage inflammatory cytokine production Daniel R. Meldrum, MD, Brian D. Shames, MD, Xianzhong Meng, MD, PhD, David A. Fullerton, MD, Robert C. McIntyre, MD, Frederick L. Grover, MD, Alden H. Harken, MD The Annals of Thoracic Surgery Volume 66, Issue 2, Pages 313-317 (August 1998) DOI: 10.1016/S0003-4975(98)00525-6

Fig 1 The effect of nitric oxide on lung macrophage tumor necrosis factor α (TNFα) production. (ETX = endotoxin; NS = not stimulated; SNAP = S-nitoso-N-acetyl-D, L-penicillamine). The Annals of Thoracic Surgery 1998 66, 313-317DOI: (10.1016/S0003-4975(98)00525-6)

Fig 2 The effect of nitric oxide on lung macrophage interleukin-1β production (ETX = endotoxin; NS = not stimulated; SNAP = S-nitoso-N-acetyl-D, L-penicillamine). The Annals of Thoracic Surgery 1998 66, 313-317DOI: (10.1016/S0003-4975(98)00525-6)

Fig 3 Representation of the initiation of lung injury after an insult and the potential mechanisms by which nitric oxide downregulates the inflammatory response. Resident lung macrophage is the first inflammatory cell type to experience an inflammatory challenge (ischemia and reperfusion, endotoxin, etc). Inciting stimuli induce lung macrophage to release the inflammatory cytokine tumor necrosis factor α (TNF) and interleukin-1β (IL-1). Tumor necrosis factor α and interleukin-1β promote lung parenchymal damage in two ways, by direct parenchymal damage through the cellular calcium dyshomeostasis or apoptosis induction and by recruitment of neutrophils that release injurious reactive oxygen metabolites. Nitric oxide (NO) may circumvent this vicious cycle by decreasing inflammatory cytokine (TNF and IL-1) production by the resident lung macrophage. Nitric oxide may inhibit inflammatory cytokine production by affecting the transcription signal (nuclear factor kappa B, NFκB) required for their production (inset). (CD14 = LPS receptor; IκB = inhibitory κB; LBP = LPS binding protein; LPS = lipopolysaccharide; mRNA = messenger ribonucleic acid.) The Annals of Thoracic Surgery 1998 66, 313-317DOI: (10.1016/S0003-4975(98)00525-6)