Studies have helped to explain how neutrophils cause connective tissue damage and, potentially, all the elastase-mediated pathologic changes. The NE is stored within neutrophil azurophil granules, where its concentration has been estimated at approximately 5 mM. Following neutrophil activation, the granules undergo exocytosis, and the enzyme diffuses away from the granule, its concentration dropping as it does so. Inhibitors such as α1-AT and secretory leukoproteinase inhibitor inactivate NE on a 1:1 mol/L basis. The concentrations of these inhibitors within the lung interstitium are unknown, however, α1-AT, for instance, is a freely diffusible molecule, and the serum protein albumin (which is the same molecular size as α1-AT) is thought to be present in the interstitium at approximately 80% of the concentration in the serum.25Since the serum concentration of α1-AT in healthy subjects is approximately 30 μM, the predicted concentration in the interstitium should be approximately 24 μM, which is some 200 times lower than the concentration of elastase in the azurophil granule. Thus, NE has to diffuse away from the granule until the concentration has fallen sufficiently for the enzyme to be completely inactivated by the local concentration of α1-AT. The relationship between the concentration of elastase and the distance away from the azurophil granule has been predicted to be exponential.26 There is a rapid fall in concentration until it reaches approximately 11 μM, and, thereafter, the concentration falls more slowly.