Characterization of serine/cysteine protease inhibitor α1-antitripsin from meconium-instilled rabbit lungs

• Published in: Journal of cellular biochemistry 2005-09, Vol.96 (1), p.137-144
• Main Authors: Zagariya, A.M., Bhat, R., Zhabotynsky, E., Chari, G., Navale, S., Xu, Q., Keiderling, T.A., Vidyasagar, D.
• Format: Article
• Language: English
• Subjects: apoptosis; cysteine; lungs; meconium; proteases; serine
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.20492

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 α1‐antitripsin. We hypothesize that serpin may attenuate pulmonary inflammation and improve surfactant function after meconium aspiration. α1‐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. α1‐antitripsin is synthesized by epithelial cells, macrophages, monocytes, and neutrophils. Deficiency in α1‐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 α1‐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.