RT Journal Article SR Electronic T1 The role of cathepsin D, H & K in the regulation of tumstatin levels in asthmatic airways JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP p3908 VO 38 IS Suppl 55 A1 Janette Burgess A1 Karryn Grafton A1 Gavin Tjin A1 Josephine Middelburg A1 Pleuntje van Egmond A1 Judith Black A1 Brian Oliver YR 2011 UL http://erj.ersjournals.com/content/38/Suppl_55/p3908.abstract AB Introduction: Angiogenesis is a prominent feature of remodelling in asthma. We previously reported that tumstatin, an endogenous angiogenic inhibitor which is the non-collagenous domain-1 (NC1) of the collagen IV α3 chain is absent from asthmatic airways. Tumstatin is released from the basement membrane by specific proteases. Cathepsins D, H and K (members of a broad family of proteases that degrade ECM proteins including collagen IV in other organs) are increased in inflammatory diseases and modulate tumour angiogenesis. We hypothesised that cathepsin D, H and/or K plays a role in the absence of tumstatin in asthmatic airways.Methods: Cathepsin mRNA expression was measured by real time RT-PCR. Immunohistochemistry was used to measure cathepsin D, H and K in human airway tissue sections. Recombinant tumstatin and airway tissue sections were digested with active recombinant cathepsin D, H and K and the resultant cleavage products analysed by polyacrylamide gel electrophoresis.Results: Human airway smooth muscle cells express cathepsin D and H mRNA. In both asthmatic and nonasthmatic airway sections inflammatory cells exhibit strong staining for cathepsin D. Cathepsin H and K are also strongly expressed in asthmatic airway tissues. Recombinant tumstatin was completely degraded by recombinant cathepsin D and H whilst cathepsin K degradation produced a 10kDa cleavage product. In human tissue sections recombinant cathepsin D completely digested tumstatin. Digestion with cathepsin K resulted in greater detection of the tumstatin antigen.Conclusion: These findings suggest that cathepsin D, H and K may play a role in the regulation of tumstatin levels in the asthmatic airways.