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Published ahead of print on May 14, 2003, doi:10.1165/rcmb.2002-0286OC

Am. J. Respir. Cell Mol. Biol., Volume 29, Number 4, October 2003, 523-530

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Submitted on December 4, 2002
Revised on May 13, 2003

Myeloid Related Protein (MRP)-8/14 Stimulates IL-8 Production in Airway Epithelial Cells

Ali Ahmad1*, Darren L Bayley1, Shiping He1, and Robert A Stockley1

1 Department of Medicine, University of Birmingham, Birmingham, United Kingdom

* To whom correspondence should be addressed. 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 IL-8, that is 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 pro-inflammatory molecules likely to be of relevance in the lung. TNF- {alpha}, IL-1 {beta} and LPS 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 LPS accounted for approximately 33% of this activity. An abundant 32kDa protein capable of stimulating IL-8 production was isolated from the secretion and identified as neutrophil cytoplasmic 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.




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