Characterization of serine/cysteine protease inhibitor alpha1-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 alpha1-antitripsin. We hypothesize that serpin may attenuate pulmonary inflammation and improve surfactant function after meconium aspiration. Alpha1-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. Alpha1-antitripsin is synthesized by epithelial cells, macrophages, monocytes, and neutrophils. Deficiency in alpha1-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 alpha1-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.
Zagariya
A M
AM
Department of Pediatrics, Division of Neonatology, The University of Illinois, Chicago, Illinois 60612, USA.
Bhat
R
R
Zhabotynsky
E
E
Chari
G
G
Navale
S
S
Xu
Q
Q
Keiderling
T A
TA
Vidyasagar
D
D
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000502:physiology; D008168:Lung / Q000502:physiology*; D008470:Meconium; D011817:Rabbits; D020539:Sequence Analysis, Protein; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000502:physiology; D017550:Spectroscopy, Fourier Transform Infrared; D000515:alpha 1-Antitrypsin / Q000737:chemistry* / Q000502:physiology*
D015853:Cysteine Proteinase Inhibitors; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin