In contrast to the alveolar spaces, only CXCL5 was decreased in the interstitial compartment of the lung in ADAM17- null mice. The greater reduction in neutrophil-tropic chemokines in the alveolar compartment of ADAM17-null mice implies a specific molecular process accounting for the lack of neutrophil transepithelial migration into the alveolar air spaces at the later time point in our study. Of additional interest is that alveolar neutrophil levels in ADAM17-null mice were initially enhanced upon inducing lung inflammation when compared to control mice. The reasons for this are not clear at this time, but may be the result of still other neutrophil chemoattractants or an enhanced ability of ADAM17-deficient neutrophils to respond to them. In conclusion, our study demonstrates for the first time that leukocyte ADAM17 regulates acute lung inflammation by modulating Neuromedin B intra-alveolar neutrophil levels and the shedding of IL-6R, L-selectin, and TNF-a. It is known that preventing TNF-a activity can increase host susceptibility to infection, and thus it will be important to determine the role of leukocyte ADAM17 in pulmonary defense against bacterial infection. Of interest is that we have recently reported that ADAM17-null mice demonstrate enhanced host resistance, including decreased hematogenous spread of bacterial to the lung, during E. coli-mediated abdominal sepsis. Human DDX3 is a member of the DEAD-box family of RNA helicases and is located on the X chromosome. DEAD-box RNA helicases have been shown to function in RNA metabolism including translation, ribosome biogenesis, pre-mRNA splicing, and nucleo-cytoplasmic RNA transport. Human DDX3 shares significant amino-acid sequence homology with orthologs from several species including yeast, Drosophila, Xenopus, and murine. Thus, natural selection of an ancestral DDX3 protein with characteristics that have been passed along to higher organisms is an indication that this protein is involved in cellular pathways that are essential to PX 12 survival. In humans DDX3 has a function in folliculogenesis as its deletion or dysfunction represents an important genetic cause of primary amenorrhea or impairment of female fertility.