Characterization of serine/cysteine protease inhibitor α 1 ‐antitripsin from meconium‐instilled rabbit lungs

We have recently purified from meconium‐instilled rabbit lungs a novel serine proteinase inhibitor, with an apparent molecular mass of 50 kDa, which we assign to be α 1 ‐antitripsin. We hypothesize that serpin may attenuate pulmonary inflammation and improve surfactant function after meconium aspiration. α 1 ‐antitripsin is a member of the proteinase inhibitor (serpin) superfamily and inhibitor of neutrophil elastase, and it can be identified as a member of the family by its amino acid sequence due to the high degree of conserved residues. α 1 ‐antitripsin is synthesized by epithelial cells, macrophages, monocytes, and neutrophils. Deficiency in α 1 ‐antitripsin leads to exposure of lungs to uncontrolled proteolytic attack from neutrophil elastase or other damaging factors culminating in lung destruction and cell apoptosis. We hypothesize that accumulation of α 1 ‐antitripsin in the lungs serves as a predisposed protection against meconium‐induced lung injury. In this paper, we show how this knowledge can lead to the development of novel therapeutic approaches for treatment of MAS. © 2005 Wiley‐Liss, Inc.