Regulation of platelet-activating factor synthesis in human monocytes by dipalmitoyl phosphatidylcholine
Tonks, Amanda J.
Society for Leukocyte Biology
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Platelet-activating factor (PAF) has a major role in inflammatory responses within the lung. This study investigates the effect of pulmonary surfactant on the synthesis of PAF in human monocytic cells. The pulmonary surfactant preparation Curosurf® significantly inhibited lipopolysaccharide (LPS)-stimulated PAF biosynthesis (P<0.01) in a human monocytic cell line, Mono mac-6 (MM6), as determined by 3H PAF scintillation-proximity assay. The inhibitory properties of surfactant were determined to be associated, at least in part, with the 1,2-dipalmitoyl phosphatidylcholine (DPPC) component of surfactant. DPPC alone also inhibited LPS-stimulated PAF biosynthesis in human peripheral blood monocytes. DPPC treatment did not affect LPS-stimulated phospholipase A2 activity in MM6 cell lysates. However, DPPC significantly inhibited LPS-stimulated coenzyme A (CoA)-independent transacylase and acetyl CoA:lyso-PAF acetyltransferase activity. DPPC treatment of MM6 cells decreased plasma membrane fluidity as demonstrated by electron paramagnetic resonance spectroscopy coupled with spin labeling. Taken together, these findings indicate that pulmonary surfactant, particularly the DPPC component, can inhibit LPS-stimulated PAF production via perturbation of the cell membrane, which inhibits the activity of specific membrane-associated enzymes involved in PAF biosynthesis
Journal of Leukocyte Biology
Tonks, A.J., Tonks, A., Morris, R.H.K., Jones, K.P. and Jackson, S.K. (2003) 'Regulation of platelet-activating factor synthesis in human monocytes by dipalmitoyl phosphatidylcholine', Journal of leukocyte biology, 74(1), pp.95-101.
This article was published in Journal of Leukocyte Biology on 22 May 2003 (online) avaialble at http://dx.doi.org/10.1189/jlb.1202601
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