Selective induction of phospholipase D1 in pathogen-activated human monocytes

• Published in: Biochemical journal Vol. 358; no. 1; pp. 119 - 125
• Main Authors: LOCATI, Massimo, RIBOLDI, Elena, BONECCHI, Raffaella, TRANSIDICO, Pietro, BERNASCONI, Sergio, HARIBABU, Bodduluri, MORRIS, Andrew J., MANTOVANI, Alberto, SOZZANI, Silvano
• Format: Journal Article
• Language: English; Japanese
• Published: 15.08.2001
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3580119

Phospholipase D (PLD) activation is part of the complex signalling cascade induced during phagocyte activation. Two PLD isoforms have been cloned, but their role in phagocyte functions is still poorly defined. We report that resting fresh circulating human monocytes expressed PLD1. PLD1 protein expression was rapidly down-regulated during cell culture. Lipopolysaccharide and pathogen-derived agonists (Candida albicans, arabinoside-terminated lipoarabinomannan and Gram-positive bacteria, but not mannose-capped lipoarabinomannan or double-stranded RNA) strongly induced PLD1 expression at both the mRNA and protein levels. Pro-inflammatory cytokines [interleukin (IL)-1β and tumour necrosis factor α] had only a weak effect, whereas immune cytokines (IL-6 and interferon γ), anti-inflammatory cytokines (IL-13 and IL-10) and chemoattractants (fMet-Leu-Phe and macrophage chemoattractant protein 1) were inactive. None of the agonists tested induced significant changes in the basal expression of PLD2 mRNA. Consistent with PLD1 up-regulation was the observation that PLD enzymic activity was higher in monocytes treated with active-pathogen-derived agonists than in control cells, when stimulated with PMA or with chemotactic agonists (fMet-Leu-Phe and C5a). Thus PLD2 seems to be a constitutive enzyme in circulating monocytes. Conversely, PLD1 is an inducible protein, rapidly regulated during culture conditions and selectively induced during cell activation. Therefore PLD1 might have a relevant role in immune responses against pathogens and in chronic inflammation.