Neutrophil DNA Contributes to the Antielastase Barrier during Acute Lung Inflammation

During acute lung inflammation, the airspaces are invaded by Neutrophils are mostly harmful through the release of their circulating neutrophils. These may then injure tissues through serine proteinases, particularly elastase (2, 7, 8). Human the release of elastase. Different natural specific inhibitors such leukocyte elastase exerts a strong tissue-damaging activity as 1-proteinase inhibitor, secretory leukocyte proteinase in- by hydrolyzing most extracellular matrix components such hibitor, and elafin are nonetheless able to counteract the enzy- as elastin, fibronectin, proteoglycan, and collagen, and also matic activity of elastase. The present study was undertaken by affecting the integrity of the endo–epithelial barrier to assess the role of these different inhibitors in the intrinsic (9–11). Indeed, increased elastase activity has been found antielastase barrier during lipopolysaccharide-induced lung inin the bronchoalveolar lavage fluids (BALF) in patients flammation in mice. Upon intranasal administration of lipopolywith ARDS (12). This prompted studies that showed that saccharide to mice, the antielastase activity recovered from bronchoalveolar lavage fluids (BALF) increases progressively up the use of structurally different elastase inhibitors was beneto 48 h (7-fold) and returns to the basal level within 72 h. ficial in models of acute lung inflammation (13). By contrast, when the same experiments are performed with Indeed, the body produces different natural specific inneutropenic mice (pretreatment with an antigranulocyte anti- hibitors to counteract the biological destructive activity of body, or vinblastine), the increase is almost totally absent. Ultra- elastase (14, 15). In lungs, one can consider two groups filtration of BALF through 100 kD cutoff membranes shows that (16): the early or alarm inhibitors such as the secretory the activity remains in the retentate, thus ruling out a role for leukocyte proteinase inhibitor (SLPI) and elafin, and the native 1-proteinase inhibitor, secretory leukocyte proteinase