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Abstract
Background: Deficiency of the antiprotease alpha-1-antitrypsin (AAT) and exposure to cigarette smoke (CS) contribute to the development of early onset emphysema. CS-induced apoptosis of alveolar cells including endothelial cells plays critical role in the lung destruction. AAT deficiency is associated with increased lung tissue destruction as well. We hypothesize that AAT protects lung alveoli from noxious environmental stimuli such as CS-induced apoptosis. Methods: Porcine pulmonary artery endothelial cells (PAEC) were exposed to CS in the presence or absence of AAT (20μ M). AAT internalization and markers for apoptosis were assessed by confocal microscopy. Flow cytometry was performed in parallel to quantify the number of AAT-loaded and apoptotic cells. Results: We demonstrated that exogenous AAT accumulated in PAEC and protected cells from CS-induced apoptosis. AAT-loaded CS-exposed cells exhibited increased amounts of chaperone HSP-70 in their cytosol and less apoptosis inducing factor in their nuclei compared to AAT-untreated, CS-exposed cells. Conclusions: Our results suggest that AAT is taken up by endothelial cells via two mechanisms and that intracellular AAT may have a protective role in CS-induced endothelial apoptosis. This may open new insights into the field of endothelial serpins as agents capable of protecting the vasculature from environment-derived noxious substances.
| Abbreviations | ||
| AAT, | = | alpha-1-antitrypsin, serpins serine protease inhibitors |
| NE | = | neutrophil elastase |
| HSP, | = | heat shock protein |
| AIF, | = | apoptosis inducing factor |
| PAEC, | = | porcine pulmonary artery endothelial cells |
| CS, | = | cigarette smoke |
| WST | = | 4-[3-(4-iodopheny)-2-(4-nitrop henyl)-2H-5-tetrazolio]-1,3-benzene disulfonate |
| MES, | = | 2-(N-morpholino) ethanesulfonic acid) |
| GPCR, | = | G-protein-coupled receptor |
| Rho, | = | Rhodamine |
| Abbreviations | ||
| AAT, | = | alpha-1-antitrypsin, serpins serine protease inhibitors |
| NE | = | neutrophil elastase |
| HSP, | = | heat shock protein |
| AIF, | = | apoptosis inducing factor |
| PAEC, | = | porcine pulmonary artery endothelial cells |
| CS, | = | cigarette smoke |
| WST | = | 4-[3-(4-iodopheny)-2-(4-nitrop henyl)-2H-5-tetrazolio]-1,3-benzene disulfonate |
| MES, | = | 2-(N-morpholino) ethanesulfonic acid) |
| GPCR, | = | G-protein-coupled receptor |
| Rho, | = | Rhodamine |