BACKGROUND: There is strong evidence that oxidative stress is associated with 
the pathogenesis of chronic obstructive pulmonary disease (COPD). The transient 
receptor potential melastatin-2 (TRPM2) is an oxidative stress sensing channel 
that is expressed in a number of inflammatory cells and therefore it has been 
suggested that inhibition of TRPM2 could lead to a beneficial effect in COPD 
patients. In this study, we have investigated the role of TRPM2 in a variety of 
mouse models of oxidative stress and COPD using TRPM2-deficent mice.
METHODS: Mice were exposed to ozone (3 ppm for 4 h) or lipopolysaccharide (LPS, 
0.3 mg/kg, intranasaly). In another model, mice were exposed to tobacco smoke 
(750 μg/l total wet particulate matter) for 30 min twice a day on three 
consecutive days. For the exacerbation model, the smoke exposure on the morning 
of day 3 animals was replaced with intranasal administration of LPS (0.3 mg/kg). 
Animals were killed 3 and 24 h after the challenge (ozone and LPS model) or 18 h 
after the last tobacco smoke exposure. In vitro neutrophil chemotaxis and 
monocyte activation were also studied using cells isolated from wild type and 
TRPM2-deficient animals. Statistical significance for the in vivo data (P < 
0.05) was determined using analysis of variance with Kruskal-Wallis and Dunns 
multiple comparison test.
RESULTS: In all models studied, no difference in the bronchoalveolar lavage 
inflammation could be evidenced when comparing wild type and TRPM2-deficient 
mice. In addition, no difference could be seen in the lung inflammation as 
assessed by the measurement of various cytokines/chemokines. Similarly in 
various in vitro cellular activation assays using isolated neutrophils and 
monocytes no significant differences could be observed when comparing wild type 
and TRPM2-deficient mice.
DISCUSSION: We have shown, in all the models tested, no difference in the 
development of airway inflammation or cell activation between TRPM2-deficient 
mice and their wild type counterparts. These results would suggest that 
inhibiting TRPM2 activity in COPD would have no anti-inflammatory effect.