RT Journal Article SR Electronic T1 IL-877 isoform in lungs of preterm infants and its processing by neutrophil serine proteases JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP p503 VO 38 IS Suppl 55 A1 Mallinath Chakraborty A1 Eamon McGreal A1 Philip Davies A1 Wendy Powell A1 Svetlana Akalovich A1 Nikolai Voitenok A1 Sailesh Kotecha YR 2011 UL http://erj.ersjournals.com/content/38/Suppl_55/p503.abstract AB Introduction: Persistent neutrophilic (PMN) lung inflammation is strongly implicated in the development of Chronic Lung Disease (CLD) of Prematurity. The 72 amino acid (a.a.) chemokine, IL-872, is a key molecule involved in attracting PMNs to sites of inflammation. The longer 77 a.a. isoform (IL-877) is less potent than IL-872 in vitro. We studied expression of IL-877 in the preterm ventilated lung and its processing by neutrophil serine proteases.Methods: IL-877 was measured by ELISA in bronchoalveolar lavage fluid (BALF) from ventilated preterm infants born at ≤32 weeks gestational age and after conversion by purified PMN serine proteases. Results were compared between the CLD (persistent inflammation) and non-CLD groups (resolved).Results: The majority of IL-8 consisted of the shorter isoforms in the preterm lung (96.3% non-CLD vs 97.1% CLD, p=ns). IL-877 expression correlated well with total IL-8 (p<0.0001) but not with gestation (p=ns).Stimulated adult airway-cells and neonatal PMNs and monocytes expressed IL-877 as the major isoform, suggesting possible expression in the lung. Preterm BALF significantly converted rhIL-877 to shorter isoforms at 18 hours (p<0.05), which was inhibited by α-1 antitrypsin (AAT). Purified neutrophil serine proteases converted IL-877 to shorter isoforms dose-dependently and over time.Conclusions: Majority of IL-8 in the ventilated preterm lung are the potent shorter isoforms. Although potentially expressed in the lung, IL-877 is probably converted to the shorter isoforms by neutrophil serine proteases. Inhibition of conversion by AAT suggests a potential therapeutic role for it in modulating inflammation in the preterm lung.