Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2004-6-21
pubmed:abstractText
Phospholipase D (PLD) plays a major role in the activation of the neutrophil respiratory burst. However, the repertoire of PLD isoforms present in these primary cells, the precise mechanism of activation, and the impact of cell priming on PLD activity and localization remain poorly defined. RT-PCR analysis showed that both PLD1 and PLD2 isoforms are expressed in human neutrophils, with PLD1 expressed at a higher level. Endogenous PLD1 was detected by immunoprecipitation and Western blotting, and was predominantly membrane-associated under control and primed/stimulated conditions. Immunofluorescence showed that PLD had a punctate distribution throughout the cell, which was not altered after stimulation by soluble agonists. In contrast, PLD localized to the phagolysosome membrane after ingestion of nonopsonized zymosan particles. We also demonstrate that tumour necrosis factor alpha greatly potentiates agonist-stimulated PLD activation, myeloperoxidase release, and superoxide anion generation, and that PLD activation occurs via a phosphatidylinositol 3-kinase-sensitive and brefeldin-sensitive ADP-ribosylation factor GTPase-regulated mechanism. Moreover, propranolol, which causes an increase in PLD-derived phosphatidic acid accumulation, caused a selective increase in agonist-stimulated myeloperoxidase release. Our results indicate that priming is a critical regulator of PLD activation, that the PLD-generated lipid products exert divergent effects on neutrophil functional responses, that PLD1 is the major PLD isoform present in human neutrophils, and that PLD1 actively translocates to the phagosomal wall after particle ingestion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2755-64
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Effect of priming on activation and localization of phospholipase D-1 in human neutrophils.
pubmed:affiliation
Respiratory Medicine Division, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Cambridge, UK. kc220@cam.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't