Lysophospholipid transacetylase in the regulation of PAF levels in human monocytes and macrophages.
The transacetylase (TA), reported to be identical to platelet-activating factor (PAF) acetylhydrolase (II), is a multifunctional enzyme with three catalytic activities: lysophospholipid transacetylase (TA(L)), sphingosine transacetylase (TA(S)), and acetylhydrolase (AH). We report that TA(L) activity participates in the control of PAF levels in monocytes and macrophages and that its regulation differs in these two types of cells. In monocytes, LPS or granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically increased the TA(L) activity. Western blot analysis and enzyme assays on immunoprecipitates revealed that the increased activity can be ascribed to PAF-AH (II) and that both translocation from cytosol to membranes and p38/ERKs-mediated phosphorylation regulate the enzyme activation. Instead, in macrophages differentiated in vitro from monocytes by incubation with FCS, an increase of both TA(L) and AH activities was observed. Moreover, activation of ERKs and p38 MAP kinase was not required for the up-regulation of PAF-AH (II) in differentiated macrophages. The differences observed in macrophages as compared to monocytes can be explained by 1) p38/ERKs-independent phosphorylation of PAF-AH (II) and 2) appearance of plasma PAF-AH in the course of macrophage differentiation.
Department of Biochemistry and Biophysics, Second University of Naples, via L. De Crecchio 7, Naples 80138, Italy.
Luigi
L
Servillo
Ciro
C
Balestrieri
Alfonso
A
Giovane
Paola
P
Pari
Davide
D
Palma
Giorgio
G
Giannattasio
Massimo
M
Triggiani
Maria Luisa
ML
Balestrieri
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism*; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism*; D021381:Protein Transport; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007527:Isoenzymes; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase