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Myeloid Related Protein-8/14 Stimulates Interleukin-8 Production in Airway Epithelial Cells

Respiratory Research Laboratory, Department of Medicine, University of Birmingham, United Kingdom

Address correspondence to: Ali Ahmad, Department of Medicine, University of Birmingham, Birmingham B15 2TT, UK. E-mail: a.ahmad{at}bham.ac.uk

Excessive neutrophil recruitment is implicated in the pathogenesis of chronic lung diseases by causing collateral tissue damage. The cells move from the circulation in response to chemokines, such as interleukin (IL)-8, that are secreted by several lung cell types including epithelial cells. This study has investigated factors present in bronchial secretions that are responsible for IL-8 expression and secretion by epithelial cells and hence initiate or perpetuate the recruitment of neutrophils. A549 epithelial cells were stimulated with proinflammatory molecules likely to be of relevance in the lung. Tumor necrosis factor-, IL-1ß, and lipopolysaccharide stimulated IL-8 production from epithelial cells in a dose- and time-dependent manner, and these effects were abrogated by specific antibodies or inhibitors. Bronchial secretions also stimulated IL-8 production, and lipopolysaccharide accounted for 33% of this activity. An abundant 32-kD protein capable of stimulating IL-8 production was isolated from the secretion and identified as neutrophil cytoplasmic protein myeloid-related protein (MRP)-14, which is the heavy polypeptide chain in the MRP-8/14 heterodimer. Abrogation of MRP-14 activity with a specific antibody also reduced the IL-8–stimulating potential of bronchial secretions, suggesting it was a significant stimulus to IL-8 production in the lung and may amplify the neutrophilic inflammation seen in bronchial disease.

Abbreviations: bovine serum albumin, BSA • enzyme-linked immunosorbent assay, ELISA • interleukin, IL • LPS-binding protein, LBP • lipopolysaccharide, LPS • myeloid-related protein, MRP • normal human bronchial epithelial cells, NHBE cells • polyvinylidene difluoride, PVDF • sodium dodecyl sulfate, SDS • saline sodium citrate, SSC • tumor necrosis factor, TNF

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