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  PLD1 rather than PLD2 regulates phorbol-ester-, adhesion-dependent and Fc{gamma}-receptor-stimulated ROS production in neutrophils

Norton, L. J., Zhang, Q., Saqib, K. M., Schrewe, H., Macura, K., Anderson, K. E., et al. (2011). PLD1 rather than PLD2 regulates phorbol-ester-, adhesion-dependent and Fc{gamma}-receptor-stimulated ROS production in neutrophils. J Cell Sci, 124(Pt 12), 1973-1983. doi:10.1242/jcs.082008.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-77F1-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-77F3-3
Genre: Journal Article

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Norton, L. J., Author
Zhang, Q.1, Author              
Saqib, K. M., Author
Schrewe, H.2, Author              
Macura, K.2, Author              
Anderson, K. E., Author
Lindsley, C. W., Author
Brown, H. A., Author
Rudge, S. A., Author
Wakelam, M. J., Author
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
2Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              

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Free keywords: Animals; Cell Adhesion/physiology; Mice; Mice, Knockout; Neutrophils/*metabolism; Phorbol Esters; Phospholipase D/antagonists & inhibitors/deficiency/genetics/*metabolism; Reactive Oxygen Species/*metabolism; Receptors, IgG/*metabolism; Signal Transduction; Tetradecanoylphorbol Acetate/pharmacology
 Abstract: The signalling lipid phosphatidic acid (PA) is generated by the hydrolysis of phosphatidylcholine (PC), which is catalysed by phospholipase D (PLD) enzymes. Neutrophils, important cells of the innate immune system, maintain the body's defence against infection. Previous studies have implicated PLD-generated PA in neutrophil function; these have relied heavily on the use of primary alcohols to act as inhibitors of PA production. The recent development of isoform-selective small molecule inhibitors and the generation of a knockout mouse model provide us with accurate tools to study the role of PLDs in neutrophil responses. We show that PLD1 is a regulator of phorbol-ester-, chemoattractant, adhesion-dependent and Fcgamma-receptor-stimulated production of reactive oxygen species (ROS) in neutrophils. Significantly we found that this role of PLD is isoform specific: the absence of PLD2 does not negatively affect these processes. Contrary to expectation, other functions required for an efficient immune response operate effectively in Pld2-deficient neutrophils or when both isoforms are inhibited pharmacologically. We conclude that although PLD1 does have important regulatory roles in neutrophils, the field has been confused by the use of primary alcohols; now that gold standard Pld-knockout mouse models are available, previous work might need to be reassessed.

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 Dates: 2011
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 584586
DOI: 10.1242/jcs.082008
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Title: J Cell Sci
Source Genre: Journal
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Pages: - Volume / Issue: 124 (Pt 12) Sequence Number: - Start / End Page: 1973 - 1983 Identifier: ISSN: 1477-9137 (Electronic) 0021-9533 (Print)