DIFFERENTIAL PROTEIN EXPRESSION IN LUNGS OF MOUSE STRAINS WITH DIFFERENT SENSITIVITY TO CIGARETTE SMOKE

Rationale: Cigarette smoke (CS) is the most prominent factor determining the increased prevalence of the emphysema. However, little is known why only a susceptible minority (8% - 16%) of heavy tobacco smokers develop a clinically significant disease. This suggests that genetic factors may modulate each individual’s risk. We recently reported strain differences in the response to CS in mice characterized by different levels of serum alpha1-proteinase inhibitor and sensitivity to oxidants. When exposed to CS, C57Bl and DBA/2 mice develop emphysema, while ICR mice do not show any parenchymal changes. Methods and Results: In order to have some information on individual factors underlying this susceptibility, we examined the global change of lung protein expression in response to CS in these strains. With a classical proteomic approach, 2D electrophoresis and mass spectrometry, several proteins have been found significantly up- and down-regulated in the different strains of mice. In particular, we identified 6 up-regulated and 8 down-regulated proteins in C57Bl mice as well as 4 up-regulated and 6 down-regulated proteins in DBA/2 mice. On the other hand, in insensitive ICR mice we found only down-regulated proteins. Proteins that underwent to oxidation after CS have been identified in these mice, by combining 2D electrophoresis and immunoblotting with specific antibodies for carbonyl groups. A different pattern of protein oxidation has been found between the strains of mice sensitive to CS. Conclusions: A series of qualitative and quantitative protein variations have been found among mouse strains with a different susceptibility to develop smoke-induced pulmonary lesions.