RT Journal Article T1 Effect of cooling on lung secretory phospholipase A2 activity in vitro, ex vivo, and in vivo A1 Autilio, Chiara A1 Shankar-Aguilera, Shivani A1 Minucci, Angelo A1 Touqui, Lhoussaine A1 De Luca, Daniele AB Hypothermia can modify surfactant composition and function. Secretory phospholipase A2 (sPLA2) hydrolyses surfactant phospholipids and is important in the pathobiology of several critical respiratory disorders. We hypothesize that sPLA2 activity might be influenced by the temperature partially explaining surfactant changes. This study aims to evaluate comprehensively the effect of hypothermia on sPLA2 activity. We measured sPLA2 activity at different temperatures, alone or combined with bile acids, in vitro (incubating human recombinant sPLA2-IIA and porcine sPLA2-IB), ex vivo (by cooling bronchoalveolar lavage samples from neonates with respiratory distress syndrome or no lung disease), and in vivo (using lavage samples obtained before and after 72 h of whole body cooling in neonates with hypoxic-ischemic encephalopathy). We also measured concentrations of various sPLA2 subtypes and natural sPLA2 inhibitors in in vivo cooled samples. Results were corrected for protein content and dilution. In vitro cooling did not show any effect of hypothermia on sPLA2. Ex vivo cooling did not alter total sPLA2 activity, and the addition of bile acids increased sPLA2 activity irrespective of the temperature and the type of sampled patient. In vivo hypothermia reduced median sPLA2 activity from 16.6 [15.2–106.7] IU/mg to 3.3 [2.7–8.5] IU/mg (P = 0.026) and mean sPLA2-IIA from 1.1 (0.8) pg/μg to 0.6 (0.4) pg/μg (P = 0.047), whereas dioleylphosphatidylglycerol increased from 8.3 (3.9)% to 12.8 (5.1)% (P = 0.02). Whole body hypothermia decreases in vivo global sPLA2 activity in bronchoalveolar lavage fluids through the reduction of sPLA2-IIA and increment of dioleylphosphatidylglycerol. This effect is absent during in vitro or ex vivo hypothermia. PB American Physiological Society SN 1522-1504 YR 2019 FD 2019-02-21 LK https://hdl.handle.net/20.500.14352/13595 UL https://hdl.handle.net/20.500.14352/13595 LA eng NO Laerdal Foundation NO Association pour le Développement et la Recherche en Néonatologie DS Docta Complutense RD 30 abr 2024