Secretory phospholipase A2 pathway in various types of lung injury in neonates and infants: a multicentre translational study

Background Secretory phospholipase A2 (sPLA2) is a group of enzymes involved in lung tissue inflammation and surfactant catabolism. sPLA2 plays a role in adults affected by acute lung injury and seems a promising therapeutic target. Preliminary data allow foreseeing the importance of such enzyme in some critical respiratory diseases in neonates and infants, as well. Our study aim is to clarify the role of sPLA2 and its modulators in the pathogenesis and clinical severity of hyaline membrane disease, infection related respiratory failure, meconium aspiration syndrome and acute respiratory distress syndrome. sPLA2 genes will also be sequenced and possible genetic involvement will be analysed. Methods/Design Multicentre, international, translational study, including several paediatric and neonatal intensive care units and one coordinating laboratory. Babies affected by the above mentioned conditions will be enrolled: broncho-alveolar lavage fluid, serum and whole blood will be obtained at definite time-points during the disease course. Several clinical, respiratory and outcome data will be recorded. Laboratory researchers who perform the bench part of the study will be blinded to the clinical data. Discussion This study, thanks to its multicenter design, will clarify the role(s) of sPLA2 and its pathway in these diseases: sPLA2 might be the crossroad between inflammation and surfactant dysfunction. This may represent a crucial target for new anti-inflammatory therapies but also a novel approach to protect surfactant or spare it, improving alveolar stability, lung mechanics and gas exchange

Myeloid I kappa B alpha Deficiency Promotes Atherogenesis by Enhancing Leukocyte Recruitment to the Plaques

Activation of the transcription factor NF-kappa B appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-kappa B inhibitor I kappa B alpha in atherosclerosis. Myeloid-specific deletion of I kappa B alpha results in larger and more advanced lesions in LDL-R-deficient mice without affecting the compositional phenotype of the plaques or systemic inflammatory markers in the plasma. We show that I kappa B alpha-deleted macrophages display enhanced adhesion to an in vitro endothelial cell layer, coinciding with an increased expression of the chemokine CCL5. Also, in vivo we found that I kappa B alpha(del) mice had more leukocytes adhering to the luminal side of the endothelial cell layers that cover the atherosclerotic plaques. Moreover, we introduce ER-MP58 in this paper as a new immunohistochemical tool for quantifying newly recruited myeloid cells in the atherosclerotic lesion. This staining confirms that in I kappa B alpha(del) mice more leukocytes are attracted to the plaques. In conclusion, we show that I kappa B alpha deletion in myeloid cells promotes atherogenesis, probably through an induced leukocyte recruitment to plaques