| http://purl.uniprot.org/citations/28362108 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28362108 | http://www.w3.org/2000/01/rdf-schema#comment | "Alpha-1 antitrypsin (AAT) deficiency-associated emphysema is largely attributed to insufficient inhibition of neutrophil elastase released from neutrophils. Correcting AAT levels using augmentation therapy only slows disease progression, and that suggests a more complex process of lung destruction. Because alveolar macrophages (Mɸ) express AAT, we propose that the expression and intracellular accumulation of mutated Z-AAT (the most common mutation) compromises Mɸ function and contributes to emphysema development. Extracellular matrix (ECM) degradation is a hallmark of emphysema pathology. In this study, Mɸ from individuals with Z-AAT (Z-Mɸ) have greater proteolytic activity on ECM than do normal Mɸ. This abnormal Z-Mɸ activity is not abrogated by supplementation with exogenous AAT and is likely the result of cellular dysfunction induced by intracellular accumulation of Z-AAT. Using pharmacologic inhibitors, we show that several classes of proteases are involved in matrix degradation by Z-Mɸ. Importantly, compared with normal Mɸ, the membrane-bound serine protease, matriptase, is present in Z-Mɸ at higher levels and contributes to their proteolytic activity on ECM. In addition, we identified matrix metalloproteinase (MMP)-14, a membrane-anchored metalloproteinase, as a novel substrate for matriptase, and showed that matriptase regulates the levels of MMP-14 on the cell surface. Thus, high levels of matriptase may contribute to increased ECM degradation by Z-Mɸ, both directly and through MMP-14 activation. In summary, the expression of Z-AAT in Mɸ confers increased proteolytic activity on ECM. This proteolytic activity is not rescued by exogenous AAT supplementation and could thus contribute to augmentation resistance in AAT deficiency-associated emphysema."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.org/dc/terms/identifier | "doi:10.1165/rcmb.2016-0366oc"xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/author | "Brantly M.L."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/author | "Wang R.L."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/author | "Rouhani F.N."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/author | "Aslanidi G."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/author | "Hoffman B.E."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/author | "Khodayari N."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/author | "Krotova K."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/author | "Marek G.W."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/name | "Am J Respir Cell Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/pages | "238-247"xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/title | "Alpha-1 Antitrypsin-Deficient Macrophages Have Increased Matriptase-Mediated Proteolytic Activity."xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://purl.uniprot.org/core/volume | "57"xsd:string |
| http://purl.uniprot.org/citations/28362108 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28362108 |
| http://purl.uniprot.org/citations/28362108 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28362108 |
| http://purl.uniprot.org/uniprot/#_A0A024R6N5-mappedCitation-28362108 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28362108 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z465-mappedCitation-28362108 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28362108 |
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| http://purl.uniprot.org/uniprot/#_A6YP93-mappedCitation-28362108 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28362108 |
| http://purl.uniprot.org/uniprot/#_A0A1L7B5J3-mappedCitation-28362108 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28362108 |
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| http://purl.uniprot.org/uniprot/#_A7L8C5-mappedCitation-28362108 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28362108 |