Augmented metalloproteinase activity and acute lung injury in copper-deficient rats

Dietary copper is required for normal function of >30 mammalian enzyme syst ems. Copper deficiency causes a number of cardiovascular defects as well as impaired immune cell function. Little is known regarding the effects of co pper deficiency on acute inflammatory responses, but this topic is relevant because many members of the Western population receive less than the recom mended dietary allowance of copper. In the current studies, we investigated the effects of dietary copper deficiency on acute lung injury induced by i ntrapulmonary deposition of IgG immune complexes. Weanling male Long-Evans rats were fed diets either adequate (5.6 mug/g) or deficient (0.3 mug/g) in copper. IgG immune complex lung injury was greatly increased in copper-def icient rats as determined by lung vascular leakage of albumin and histopath ology. However, no change was observed in either the lung content of tumor necrosis factor-alpha or lung neutrophil accumulation. Lungs from copper-de ficient rats had much higher levels of matrix metalloproteinase (MMP)-2 and MMP-9 than did copper-adequate control animals. This increased activity wa s not attributable to alveolar macrophages or neutrophils. These data sugge st that the augmented lung injury caused by copper deficiency is due to inc reased pulmonary MMP-2 and MMP-9 activity and not a generalized amplificati on of the inflammatory response.