Document Detail


Activation of primary human monocytes by the oxidized form of alpha1-antitrypsin.
MedLine Citation:
PMID:  10713080     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The oxidation of methionine residues in many proteins, including the serine proteinase inhibitor alpha1-antitrypsin (AAT), can result in functional inactivation. In this study we investigated the pro-inflammatory properties of oxidized AAT (oxAAT), specifically its ability to activate human monocytes in culture. Monocytes stimulated with oxAAT at concentrations up to 0.2 mg/ml for 24 h showed significant elevation in monocyte chemoattractant protein-1, cytokine interleukin-6, and tumor necrosis factor-alpha expression and increased NADPH oxidase activity. Monocytes activated with oxAAT showed surprising effects on lipid metabolism. Expression of low density lipoprotein (LDL) receptors increased by up to 76% compared with controls but was not accompanied by any changes in (125)I-labeled LDL binding and, paradoxically, decreased LDL uptake, degradation, and intracellular cholesterol synthesis. oxAAT also down-regulated the scavenger receptor CD36, which takes up and is up-regulated by oxidized LDL and is down-regulated by cholesterol efflux. As a by-product of oxidative events accompanying inflammation, oxAAT has multiple effects on cytokine expression, generation of reactive oxygen species, and on intracellular lipid metabolism. The up-regulation of monocyte-derived reactive oxygen by oxAAT could potentially result in self-amplification of AAT oxidation and, thereby, the other effects deriving from it. This implies that there are as yet unidentified regulatory processes that control this cycle.
Authors:
F Moraga; S Janciauskiene
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-12     Completed Date:  2000-04-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7693-700     Citation Subset:  IM    
Affiliation:
Gastroenterology-Hepatology Section, Department of Medicine, University Hospital Malmö, 20502 Malmö, Sweden.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antigens, CD36 / biosynthesis
Chemokine CCL2 / biosynthesis
Cholesterol / biosynthesis
Down-Regulation
Enzyme Activation
Humans
Inflammation Mediators / metabolism
Interleukin-6 / biosynthesis
Lipoproteins, LDL / metabolism
Membrane Proteins*
Monocytes / drug effects*
NADPH Oxidase / metabolism
Oxidation-Reduction
Receptors, Immunologic / biosynthesis
Receptors, LDL / biosynthesis
Receptors, Lipoprotein*
Receptors, Scavenger
Scavenger Receptors, Class B
Tumor Necrosis Factor-alpha / biosynthesis
alpha 1-Antitrypsin / chemistry,  pharmacology*
Chemical
Reg. No./Substance:
0/Antigens, CD36; 0/Chemokine CCL2; 0/Inflammation Mediators; 0/Interleukin-6; 0/Lipoproteins, LDL; 0/Membrane Proteins; 0/Receptors, Immunologic; 0/Receptors, LDL; 0/Receptors, Lipoprotein; 0/Receptors, Scavenger; 0/Scarb1 protein, mouse; 0/Scavenger Receptors, Class B; 0/Tumor Necrosis Factor-alpha; 0/alpha 1-Antitrypsin; 57-88-5/Cholesterol; EC 1.6.3.1/NADPH Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  O(2) sensing by airway chemoreceptor-derived cells. Protein kinase c activation reveals functional e...
Next Document:  Design of peptides with high affinities for heparin and endothelial cell proteoglycans.