We found that ex-smokers without emphysema had higher expression of CD46 in their lungs compared to emphysema/COPD patients, that also occurred in vivo in the murine smoking model of COPD where CD46 down regulation was accompanied with accumulation of C3b co-precipitated with elastin and increased C5a which in return suppressed secretion of IL12, from macrophages, stimulated by the cigarette smoke. This evidence concerns the gene C3 and chronic obstructive pulmonary disease.