title: Role of distinct phospholipases A2 and their modulators in meconium aspiration syndrome in human neonates.
abstract: OBJECTIVE
  Meconium aspiration syndrome (MAS) is a life-threatening neonatal lung injury, whose pathophysiology has been mainly studied in animal models. In such models, pancreatic secretory phospholipase A2 (sPLA2-IB) and proinflammatory cytokines present in meconium challenge the lungs, catabolising surfactant and harming the alveoli. Locally produced phospholipases might perpetuate the injury and influence clinical pictures and therapeutic approaches. Our aim is to verify whether pulmonary phospholipase A2 (sPLA2-IIA) is involved in the damage and to determine if phospholipases and their modulators are associated with MAS clinical pictures.
  
  
  METHODS
  We studied distinct phospholipases A2 and their modulators in broncho-alveolar lavage (BAL) fluids and in meconium of five MAS neonates and in five control neonates ventilated for extrapulmonary reasons.
  
  
  RESULTS
  MAS patients have higher amounts of pulmonary phospholipase (sPLA2-IIA; P = 0.016) and Clara cell secretory protein (CCSP; P = 0.032). The local production of such proteins by the lung is confirmed by their very low levels in meconium. sPLA2-IIA contributes to the higher total enzyme activity in MAS patients, as compared to controls (P = 0.008). Cytosolic phospholipase was not detected in meconium or alveolar fluid. sPLA2 activity and sPLA2-IIA concentrations are correlated with the TNFα and with the release of CCSP. sPLA2 total activity, sPLA2-IIA and TNFα concentrations in BAL fluids correlate with the oxygenation impairment and haemorrhagic lung oedema.
  
  
  CONCLUSIONS
  Pulmonary sPLA2 is locally produced and contributes to the total sPLA2 activity during MAS. CCSP is also produced in trying to lower the inflammation. Both sPLA2 activity and sPLA2-IIA are significantly correlated with oxygenation impairment and haemorrhagic lung oedema.
authors.affiliation: Laboratory of Clinical Molecular Biology, Institute of Biochemistry, Servizio Analisi 1, University Hospital A. Gemelli, Catholic University of the Sacred Heart, L.go A. Gemelli 8, 00168, Rome, Italy. dm.deluca@fastwebnet.it
authors.forename: Daniele
authors.initials: D
authors.lastname: De Luca
authors.forename: Angelo
authors.initials: A
authors.lastname: Minucci
authors.forename: Domenico
authors.initials: D
authors.lastname: Tripodi
authors.forename: Marco
authors.initials: M
authors.lastname: Piastra
authors.forename: Domenico
authors.initials: D
authors.lastname: Pietrini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zuppi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Conti
authors.forename: Virgilio P
authors.initials: VP
authors.lastname: Carnielli
authors.forename: Ettore
authors.initials: E
authors.lastname: Capoluongo
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008471:Meconium Aspiration Syndrome / Q000201:enzymology* / Q000503:physiopathology; D054467:Phospholipases A2 / Q000378:metabolism*; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014598:Uteroglobin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D014598:Uteroglobin; D054467:Phospholipases A2