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Published ahead of print on June 2, 2009
Am. J. Respir. Cell Mol. Biol. 2009, doi:10.1165/rcmb.2009-0078OC
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Submitted on March 1, 2009
Accepted on June 1, 2009

A Specific Phospholipase C Activity Regulates Phosphatidylinositol Levels in Lung Surfactant of ARDS Patients

Spyros Spyridakis1, George Leondaritis1, George Nakos2, Marilena E Lekka3, and Dia Galanopoulou4*

1 Chemistry, University of Athens, Athens, Greece, 2 University Hospital of Ioannina, University of Ioannina, Medical School, Ioannina, Greece, 3 Chemistry, University of Ioannina, Ioannina, Greece, 4 Chemistry, University of Athens, Zografou, Athens, 15771, Greece

* To whom correspondence should be addressed. E-mail: galanopoulou{at}chem.uoa.gr.

Lung Surfactant (LS) is a lipid-rich material lining the inside of the lungs. It reduces surface tension at the liquid/air interface and thus, it confers protection of the alveoli from collapsing. The surface-active component of LS is dipalmitoyl-phosphatidylcholine, while anionic phospholipids such as phosphatidylinositol (PtdIns) and primarily phosphatidylglycerol are involved in the stabilization of the LS monolayer. The exact role of PtdIns in this system is not well-understood; however, PtdIns levels change dramatically during the Acute Respiratory Distress Syndrome (ARDS) evolution. In this report we present evidence of a phosphoinositide-specific phospholipase C (PI-PLC) activity in Bronchoalveolar Lavage (BAL) fluid which may regulate PtdIns levels. Characterization of this extracellular activity showed specificity for PtdIns and phosphatidylinositol 4,5-bisphosphate, sharing the typical substrate concentration-, pH- and calcium-dependencies with mammalian PI-PLCs. Fractionation of BAL fluid showed that PI-PLC did not co-fractionate with large surfactant aggregates, but it was found mainly in the soluble fraction. Importantly, analysis of BAL samples from control and ARDS patients showed that the PI-PLC specific activity was decreased by 4-fold in ARDS samples concurrently with the increase in BAL PtdIns levels. Thus, we have identified for the first time an extracellular PI-PLC enzyme activity which may be acutely involved in the regulation of PtdIns levels in LS.
Key words: phospholipase C • phosphatidylinositol • phosphatidylinositol 4,5-bisphosphate • lung surfactant • ARDS






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