RT Journal Article
SR Electronic
T1 Granzyme B expression in lung of fatal asthmatics
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p468
VO 38
IS Suppl 55
A1 Yvonne Nussbaumer-Ochsner
A1 Luiz Silva
A1 Annemarie van Schadewijk
A1 Marisa Dolhnikoff
A1 Thais Mauad
A1 Klaus Rabe
A1 Pieter Hiemstra
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p468.abstract
AB Introduction: Granzymes are serine proteases mainly produced by CD8 and NK cells, and are involved in the pathogenesis of many inflammatory disorders. Granzyme B (GzmB) is released towards target cells, but can also be released nonspecifically and is capable of cleaving extracellular matrix (ECM) components contributing to ECM degradation and remodeling in chronic inflammation. Recent studies have also shown participation of GzmB in allergic inflammation, but there are no descriptions of the its expression in fatal asthmatics.Methods: We studied large and small airways and lung parenchyma of 12 patients that died of fatal asthma (FA) and 8 controls (CTR). Using image analysis we measured the number of GzmB positive cells in the inner layer (IL), smooth muscle (SM) and outer layer (OL) of both large (LA) and small airways (SA) and in peribronchiolar (PS) and distal (DS) alveolar septa. Values [median (IQR)] were expressed as GmzB+ cells/BM length (cells/mm) in OL and IL, GmzB+ cells/SM area (cells/mm2) in SM, and as GmzB+ cells/septal length (cells/μm) in PS and DS.Results: In LA we found a higher number of GmzB+ cells in IL [FA=12.9 (5.1), CTR=5.8 (3.1), p=0.02)] and OL ([FA=27.2 (9.3), CTR=7.5 (2.4), p=0.001)] in FA, but no differences were observed in SM. In SA, the number of GmzB+ cells was also higher in IL [FA=8.3 (4.4), CTR=2.8 (1.8), (p=0.03)] and OL [FA=15.9 (5.3), CTR=5.2 (4.1), (p=0.002)] in FA, but no differences were observed in SM. In the parenchyma, there was a higher number of GmzB+ cells in PS of FA comparing to CTR (p=0.02), but no differences were observed in DS.Conclusion: The results show that GzmB expression is increased in FA and may contribute to the previously described process of airway remodeling in these patients.