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Role of distinct phospholipases A2 and their modulators in meconium aspiration syndrome in human neonates

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Abstract

Purpose

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.

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Acknowledgments

The authors are grateful to Joaquim Trias (PhD) and Chiara Campana (MD) for the critical review of manuscript and English style. They also thank Michal Karpisek (PhD) for his collaboration in the cross-reactivity test and for kindly providing human recombinant sPLA2-IIA. This study was funded by QProgetti Ltd (Roma, Italy; grant 1-2/2010) and NeoSal Foundation (Ancona, Italy). These institutions financed the research as charity programs and had no role either in the project or in the development of the study and data management.

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Authors and Affiliations

  1. 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

    Daniele De Luca, Angelo Minucci, Domenico Tripodi, Cecilia Zuppi & Ettore Capoluongo

  2. Neonatal Intensive Care Unit, Institute for Child Health, Women’s and Children Hospital “G. Salesi”, Polytechnical University of Marche, Ancona, Italy

    Daniele De Luca & Virgilio P. Carnielli

  3. Pediatric Intensive Care Unit, Department of Anaesthesiology and Intensive Care, University Hospital “A. Gemelli”, Catholic University of the Sacred Heart, Rome, Italy

    Marco Piastra, Domenico Pietrini & Giorgio Conti

Authors
  1. Daniele De Luca
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  2. Angelo Minucci
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  3. Domenico Tripodi
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  4. Marco Piastra
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  6. Cecilia Zuppi
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  7. Giorgio Conti
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  8. Virgilio P. Carnielli
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  9. Ettore Capoluongo
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Correspondence to Daniele De Luca.

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De Luca, D., Minucci, A., Tripodi, D. et al. Role of distinct phospholipases A2 and their modulators in meconium aspiration syndrome in human neonates. Intensive Care Med 37, 1158–1165 (2011). https://doi.org/10.1007/s00134-011-2243-z

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  • DOI: https://doi.org/10.1007/s00134-011-2243-z

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