Role of Serine Proteases in the Regulation of Interleukin-8.sub.77 during the Development of Bronchopulmonary Dysplasia in Preterm Ventilated Infants

• Published in: PloS one 2014-12, Vol.9 (12)
• Main Authors: Chakraborty, Mallinath, McGreal, Eamon P, Williams, Andrew, Davies, Philip L, Powell, Wendy, Abdulla, Salima, Voitenok, Nikolai N, Hogwood, John, Gray, Elaine, Spiller, Brad, Chambers, Rachel C, Kotecha, Sailesh
• Format: Article
• Language: English
• Subjects: Bronchopulmonary dysplasia; Interleukins; Laws, regulations and rules; Premature infants; Serine; Thrombin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0114524

The chemokine interleukin-8 is implicated in the development of bronchopulmonary dysplasia in preterm infants. The 77-amino acid isoform of interleukin-8 (interleukin-8.sub.77) is a less potent chemoattractant than other shorter isoforms. Although interleukin-8.sub.77 is abundant in the preterm circulation, its regulation in the preterm lung is unknown. To study expression and processing of pulmonary interleukin-8.sub.77 in preterm infants who did and did not develop bronchopulmonary dysplasia. Total interleukin-8 and interleukin-8.sub.77 were measured in bronchoalveolar lavage fluid from preterm infants by immunoassay. Neutrophil serine proteases were used to assess processing. Neutrophil chemotaxis assays and degranulation of neutrophil matrix metalloproteinase-9 were used to assess interleukin-8 function. Shorter, potent, isoforms interleukin-8 predominate in the preterm lung, and are increased in infants developing bronchopulmonary dysplasia, due to conversion of interleukin-8.sub.77 by neutrophil serine proteases and thrombin. Processing of interleukin-8 provides an attractive therapeutic target to prevent development of bronchopulmonary dysplasia.