A copper-deficient, zinc-supplemented diet produces emphysema in pigs.
A mild form of emphysema was produced in pigs raised on a copper-deficient, zinc-supplemented diet. The copper-requiring enzyme, lysyl oxidase, catalyzes the cross-linking of tropoelastin into mature elastin. Zinc further inhibits the activity of lysyl oxidase. Lungs from animals raised on copper-deficient, zinc-supplemented diets of demonstrate perforations in alveolar walls and diminished amounts of elastin bronchi and pulmonary arteries. Mean linear intercepts are greater and alveolar internal surface areas are less than those in control animals, fulfilling the generally accepted definition of emphysema. Physiologic confirmation is provided by a leftward shift of the saline volume-pressure curves when compared with those in control animals. Ultrastructurally, the alveolar walls are effaced and pores of Kohn are enlarged. There are areas in which elastin is absent leaving remnant microfibrils, and there are other changes consistent with active elastin synthesis. Biochemical data demonstrate no difference in elastin content as micrograms/ml of fat-free dry weight but do demonstrate increased collagen content in experimental animal lungs compared with that in control lungs. Ultrastructural similarities to enzyme-induced models of emphysema suggest the presence of elastin degradation in our model. We speculate that although the copper-deficient, zinc-supplemented state may stimulate protein synthesis in general, elastin is being degraded by endogenous means, but collagen is not.
D000399:Air Pressure; D000818:Animals; D003094:Collagen / Q000032:analysis; D003300:Copper / Q000172:deficiency*; D004032:Diet; D004195:Disease Models, Animal; D004549:Elastin / Q000032:analysis; D008168:Lung / Q000648:ultrastructure; D008176:Lung Volume Measurements; D009929:Organ Size; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D013552:Swine; D015032:Zinc / Q000494:pharmacology*
D003300:Copper; D003094:Collagen; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase; D015032:Zinc