Expression of phospholipases A2 in primary human lung macrophages: role of cytosolic phospholipase A2-alpha in arachidonic acid release and platelet activating factor synthesis.
Macrophages are a major source of lipid mediators in the human lung. Expression and contribution of cytosolic (cPLA(2)) and secreted phospholipases A(2) (sPLA(2)) to the generation of lipid mediators in human macrophages are unclear. We investigated the expression and role of different PLA(2)s in the production of lipid mediators in primary human lung macrophages. Macrophages express the alpha, but not the zeta isoform of group IV and group VIA cPLA(2) (iPLA(2)). Two structurally-divergent inhibitors of group IV cPLA(2) completely block arachidonic acid release by macrophages in response to non-physiological (Ca(2+) ionophores and phorbol esters) and physiological agonists (lipopolysaccharide and Mycobacterium protein derivative). These inhibitors also reduce by 70% the synthesis of platelet-activating factor by activated macrophages. Among the full set of human sPLA(2)s, macrophages express group IIA, IID, IIE, IIF, V, X and XIIA, but not group IB and III enzymes. Me-Indoxam, a potent and cell impermeable inhibitor of several sPLA(2)s, has no effect on arachidonate release or platelet-activating factor production. Agonist-induced exocytosis is not influenced by cPLA(2) inhibitors at concentrations that block arachidonic acid release. Our results indicate that human macrophages express cPLA(2)-alpha, iPLA(2) and several sPLA(2)s. Cytosolic PLA(2)-alpha is the major enzyme responsible for lipid mediator production in human macrophages.
Giannattasio
Giorgio
G
Department of Clinical Immunology and Allergy and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.
Lai
Ying
Y
Granata
Francescopaolo
F
Mounier
Carine M
CM
Nallan
Laxman
L
Oslund
Rob
R
Leslie
Christina C
CC
Marone
Gianni
G
Lambeau
Gérard
G
Gelb
Michael H
MH
Triggiani
Massimo
M
D016718:Arachidonic Acid / Q000378:metabolism*; D002219:Carbamates / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D015200:Fluoroimmunoassay; D005966:Glucuronidase / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007212:Indolizines / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction
D002219:Carbamates; D004791:Enzyme Inhibitors; D007212:Indolizines; D007476:Ionophores; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; C119389:indoxam; D016718:Arachidonic Acid; D054513:Group IV Phospholipases A2; D005966:Glucuronidase