The fifth component of complement (C5) is necessary for maximal pulmonary leukocytosis in mice chronically exposed to cigarette smoke.
Recruitment of elastase-containing leukocytes to the alveoli and small airways of cigarette smokers is thought to be a major contributing factor in the pathogenesis of pulmonary emphysema. The fifth component of complement (C5), when activated, acts as a potent chemoattractant for these cells. We therefore examined the effect of chronic cigarette smoke exposure on numbers of pulmonary leukocytes in congenic strains of C5-deficient (C5-) and C5-sufficient (C5+) mice. Animals were exposed daily to 15 puffs (1.5 cigarettes) or unfiltered smoke from 2A1 Kentucky Reference cigarettes. After 8 weeks of exposure, the total number of bronchoalveolar leukocytes, recovered by lavage, was significantly increased in cigarette smoke-exposed animals (both C5- and C5+) vs their sham-exposed counterparts. In addition, cigarette smoke exposure also significantly increased the total number of recovered alveolar polymorphonuclear leukocytes (PMNs) and the PMN chemotactic activity of cell-free bronchoalveolar lavage supernatants in both strains vs those of sham controls. However, total numbers of recovered bronchoalveolar leukocytes and PMNs in smoke-exposed animals were significantly greater (P less than 0.001) in C5+ mice than in their congenic C5- counterparts. In C5+ mice, acute smoke exposure caused an immediate but transient increase in chemotactic activity of lung fluids, which was not observed in C5- mice following acute smoke exposure. These results suggest that cigarette smoking induces an increase in leukocytes in the lungs of mice by mechanisms which are partly dependent on C5.
D000818:Animals; D002634:Chemotaxis, Leukocyte; D003182:Complement C5 / Q000502:physiology*; D007964:Leukocytosis / Q000503:physiopathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000276:immunology; D011650:Pulmonary Alveoli / Q000166:cytology; D012907:Smoking
D003182:Complement C5