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. Here, CD46 is linked to chronic obstructive pulmonary disease.