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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 #156835
Title: PROINFLAMMATORY EFFECTS OF COPPER DEFICIENCY ON NEUTROPHILS AND LUNG ENDOTHELIAL CELLS

Author
item LOMINADZE, DAVID - UNIV OF LOUISVILLE
item Saari, Jack
item PERCIVAL, SUSAN - UNIV OF FLORIDA
item SCHUSCHKE, DALE - UNIV OF LOUISVILLE

Submitted to: Immunology and Cell Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/24/2003
Publication Date: 6/1/2004
Citation: Lominadze, D., Saari, J.T., Percival, S.S., Schuschke, D.A. 2004. Proinflammatory effects of copper deficiency on neutrophils and lung endothelial cells. Immunology and Cell Biology. 82:231-238.

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 inflammatory response involves activation of the immune system, which includes adhesion of white blood cells to the blood vessel wall and subsequent migration of white cells across the vessel wall into the tissue and to the site of injury. The purpose of this study was to examine isolated aspects of this sequence for Cu-dependence and molecular mechanism. White cells from Cu-deficient rats contained higher amounts of a specific molecule that promotes adhesion of white blood cells to the lining cells (endothelium) of blood vessels, adhered better to a surface containing an adhesion molecule normally present on blood vessel endothelial cells, and migrated faster across a layer of endothelial cells from lung blood vessels. Endothelial cells from lung blood vessels that were made Cu-deficient by extracting Cu from them had a greater alteration of a contractile protein that promotes movement of white cells across them. These findings provide evidence for the enhancement of several phases of the inflammatory process by Cu deficiency and point to specific affected molecules that could mediate the enhancement. These findings add to our understanding of how dietary copper deficiency alters cardiovascular function as it is related to inflammation.

Technical Abstract: Dietary copper deficiency increases the accumulation of circulating neutrophils in the rat lung microcirculation. This process includes neutrophil adhesion to, migration along, and emigration through the vascular endothelium. The current study was designed to study the role of copper in each of these steps. Neutrophils were isolated from rats fed either a copper-adequate (CuA, 6.1 µg Cu/g diet) or copper-deficient diet (CuD, 0.3 µg Cu/g diet) for 4 wks. First, transient and firm adhesion of neutrophils to P-selection in a flow chamber showed there were more adhered CuD neutrophils than CuA ones. This effect is probably caused by the increased expression of CD11b that was observed in the current study. Second, the evaluation of neutrophil migration under agarose showed that the CuD neutrophils moved farther than the CuA group in response to IL-8 but not fMLP; this suggests an increased sensitivity to a CD11/CD18-independent signaling pathway. Third, the contractile mechanism of endothelial cells was studied. Elevated F-actin formation in Cu-chelated lung microvascular endothelial cells suggests that neutrophil migration may be promoted by enhanced cytoskeletal reorganization of the endothelium during copper deficiency. Combined, these results support the theory that dietary copper deficiency has proinflammatory effects on both neutrophils and the microvascular endothelium that promote neutrophil-endothelial interactions.