Figure 2: Working mechanisms underlying NAMPT in the susceptibility and pathogenesis of acute lung injury. In the case of lung insults, mechanic and/or inflammatory stimuli via NF-kappa B or other pathways dramatically increase NAMPT expression from pulmonary alveolar epithelial cells, vascular endothelial cells, inflammatory cells and other cells in those patients carrying a susceptible haplotype GC[HT:GC] in their NAMPT gene promoters, which in turn mediates NAD dependent Sirtuins or other pathways intracellularly or extracellularly to markedly increase the production of other molecular activators. These lead to pulmonary barrier permeability increase, resulting in ALI. On the contrary, when patients, who carry a protective haplotype [HT:TT] in their NAMPT gene promoters, are subjected to those same insults, less NAMPT is expressed, less molecular activators produced, thus protecting against pulmonary barrier dysfunction and reducing risk to ALI. Those dashed lines indicate that more molecular dots need to be connected. The question mark denotes the unanswered question. NAMPT-R, NAMPT receptor. Refer to the text for the detail.