Linked Life Data

8187807

Source:http://linkedlifedata.com/resource/pubmed/id/8187807

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-6-23
pubmed:abstractText
Neutrophil polymorphonuclear leukocytes (PMN) can inactivate the PMN-elastase inhibitor alpha-1-antitrypsin (A1AT) proteolytically, by using metalloproteinases normally stored as zymogens in myeloperoxidase (MPO)-negative granules. Supernatants from opsonized zymosan (OPZ)-triggered human PMN cleaved and inactivated human A1AT through a process inhibitable by metal-chelators, suggesting that the interaction of PMN with OPZ leads to the extracellular availability of active metalloenzymes. During OPZ-triggering, PMN used approximately 80% of the generated hydrogen peroxide (H2O2) to produce HOCl by means of the MPO pathway, while the remainder was catabolized by PMN themselves. No H2O2 was available as free compound in the extracellular environment and hydroxyl (.OH) or .OH-like radicals were not generated. The selective deletion of single components of the HOCl-generating MPO pathway resulted in the generation of PMN supernatants free of active metalloenzymes but rich of the corresponding zymogens. Similar results were obtained by replacing normal PMN with cells from a patient with hereditary MPO deficiency. No evidence was obtained for the intervention or contribution of .OH-like radicals, serine-proteinases and oxidized glutathione in the transformation of the zymogens into enzymes able to inactivate A1AT. On concluding, PMN undergoing phagocytosis release MPO in amount sufficient to handle the extracellular pool of the generated H2O2 entirely, leading to the generation of equimolar amounts of HOCl. In turn, HOCl or a similar compound derived from it interacts with concomitantly released metallozymogens, switching on their A1AT inactivating potential without the apparent contribution of other PMN-derived molecules.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-2972
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Proteolytic inactivation of alpha-1-antitrypsin by human neutrophils: involvement of multiple and interlinked cell responses to phagocytosable targets.
pubmed:affiliation
Department of Internal Medicine, University of Genova Medical School, Italy.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't