Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
1992-1-13
pubmed:abstractText
Although the role of tumor necrosis factor-alpha (TNF) as mediator of inflammation is now well established, its interactions with polymorphonuclear neutrophils (PMN) are not fully understood. Therefore, we investigated the possible hydrolytic action on TNF of intra-lysosomal enzymes released by activated PMN in the extracellular medium. We first incubated 125I radiolabeled TNF in vitro with activated PMN and by HPLC analysis, we observed a degradation process completely blocked by the previous addition of alpha 1-Antitrypsin (AT) to the incubation medium. By comparing several degradative patterns of TNF obtained with purified leukocyte proteases and supernatant of activated PMN, we identified elastase as the major enzyme involved in this catabolic process of TNF. In a second part, we determined the bioactivity of the cleavage fragments of recombinant human TNF (rhTNF) by a cytotoxicity assay. None of the fragments was found biologically active. Our results suggest that, at inflammatory sites, an enzymatic degradation of TNF may occur in the pericellular area of activated PMN. This new catabolic pathway leading to inactivation of TNF might be regarded as an effective local negative feed-back process limiting the potentially toxic effects of this cytokine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1879-86
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Enzymatic degradation of tumor necrosis factor by activated human neutrophils: role of elastase.
pubmed:affiliation
Laboratoire Pluridisciplinaire de Recherche Expérimentale Biomédicale, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't