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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #135448


item Saari, Jack

Submitted to: Journal of Inflammation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/12/2002
Publication Date: 12/1/2002
Citation: Schuschke, D.A., Percival, S.B., Lominadze, D., Saari, J.T., Lentsch, A.B. 2002. Tissue specific ICAM-1 expression and neutrophil transmigration in the copper-deficient rat. Inflammation. 26:297-303.

Interpretive Summary: Dietary copper (Cu) restriction causes an enhanced vulnerability to inflammation in laboratory animals as indicated by exaggeration of tissue swelling, blood vessel dilation and low blood pressure in response to inflammatory stimuli. The purpose of this study was to examine further the mechanism of this increased inflammation. We found that rats made Cu-deficient for 5 weeks had higher levels in their lungs of an enzyme (myeloperoxidase) that is used to indicate invasion of white cells, a sign of increased inflammation. In lungs and hearts of Cu-deficient rats, a molecule (ICAM-1) that promotes adhesion of white blood cells to the lining cells (endothelium) of blood vessels and therefore enhances invasion of white cells, is increased relative to tissues from Cu-adequate rats. Isolated endothelial cells from which Cu had been removed also showed higher ICAM-1 content than Cu-adequate cells, agreeing with the whole-animal experiments. When these cells were grown and treated to form a continuous layer across which white cells passage could be measured, Cu-depleted cells allowed a higher rate of passage of white cells than did Cu-adequate cells. Taken together, these studies indicate that copper deficiency enhances interactions between blood vessels and white blood cells that contribute to increased invasion of white cells into tissue and, therefore, increased inflammation. These findings add to our understanding of how dietary copper deficiency alters cardiovascular function at the level of the smallest blood vessel.

Technical Abstract: Dietary copper deficiency promotes neutrophil accumulation in rat lungs. We have now investigated the potential mechanisms of this effect. Male weanling rats were fed a Cu-adequate (6.0 mg Cu/kg diet) or Cu-deficient diet (0.30 mg Cu/kg) for 4 wks. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was measured in vivo and in vitro using a radiolabeled monoclonal antibody to rat ICAM-1. Tissue neutrophil accumulation was measured by myeloperoxidase (MPO) content and neutrophil transendothial migration was assessed in vitro. Dietary copper deficiency had no effects on the expression of ICAM-1 in lung, liver, heart, kidney, or cremaster. However, MPO content was significantly greater in the lungs of copper-deficient rats. Endotoxin-induced ICAM-1 expression was greater in the lungs and hearts of copper-deficient rats. Similarly, cultured rat endothelial cells that were Cu-chelated expressed more ICAM-1 after endotoxin. This copper dependence of ICAM-1 expression correlated with the significant increase in MPO in lungs of copper-deficient rats treated with endotoxin. The results suggest a tissue-specific difference in ICAM-1 expression and neutrophil accumulation during inflammation in copper-deficient rats. The findings suggest that lung inflammatory mechanisms are particularly sensitive to copper deficiency.