PT  - JOURNAL ARTICLE
AU  - Arlene Glasgow
AU  - Donna Small
AU  - Aaron Scott
AU  - Denise McLean
AU  - Nicolas Camper
AU  - Umar Hamid
AU  - Shauna Hegarty
AU  - Cecilia O'Kane
AU  - Danny McAuley
AU  - Fionnuala Lundy
AU  - Stuart Elborn
AU  - Sinéad Weldon
AU  - Cliff Taggart
TI  - A role for the WFDC protein, WAP2, in regulation of innate host defence in the lung
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - 4850
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/4850.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/4850.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Secretory leukocyte protease inhibitor (SLPI) and elafin are members of the WAP Four-Disulphide-Core (WFDC) family of proteins and have multiple contributions to innate immunity including inhibition of neutrophil serine proteases, antimicrobial properties and inhibition of the inflammatory response to LPS. The aims of this research were to explore potential activities of WAP2, a previously uncharacterised WFDC protein expressed in the lung. Recombinant expression and purification of WAP2 were optimised in E. coli for use in a range of functional assays. Protease activity assays were used to test antiprotease activity of rWAP2. THP-1 monocytic cells were stimulated with LPS alone or rWAP2 in combination with LPS; cytokine levels in cell-free supernatants were subsequently analysed by ELISA. To test if WAP2 could become cross-linked to extracellular matrix proteins, rWAP2 was incubated with fibronectin +/- transglutaminase, and then assessed by SDS-PAGE and Western blotting. WAP2 expression was investigated in human lung tissue sections via immunohistochemistry. Recombinant WAP2 inhibited cathepsin G activity. Monocytic cells pre-treated with rWAP2 before LPS stimulation showed significantly lower levels of IL-8 and MCP-1 production compared to cells stimulated with LPS alone. Recombinant WAP2 was conjugated to fibronectin in a transglutaminase-mediated reaction and retained antiprotease activity. WAP2 was detected in human lung tissue sections via immunohistochemistry. Together these results suggest a role for WAP2 in innate host defence. Further characterisation is required to fully understand the implications of WAP2 properties and its clinical significance.