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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 #179029
Title: IMPAIRED DEFORMABILITY OF COPPER-DEFICIENT NEUTROPHILS

Author
item GORDON, SHARON - UNIV OF LOUISVILLE, KY
item LOMINADZE, DAVID - UNIV OF LOUISVILLE, KY
item Saari, Jack
item LENTSCH, ALEX - UNIV OF CINCINNATI, OH
item SCHUSCHKE, DALE - UNIV OF LOUISVILLE, KY

Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/27/2005
Publication Date: 9/1/2005
Citation: Gordon, S.A., Lominadze, D., Saari, J.T., Lentsch, A.B., Schuschke, D.A. 2005. Impaired deformability of copper-deficient neutrophils. Experimental Biology and Medicine. 230:543-548.

Interpretive Summary: Neutrophils (white blood cells with immune function) accumulate in the lungs of animals fed copper (Cu)-deficient diet, which contributes to the pro-inflammatory nature of dietary Cu deficiency. The purpose of this study was to examine two possible mechanisms for this occurrence. First, the chemical attraction for neutrophils in the lung was examined by measuring the lung concentration of MIP-2, a specific chemical that is known to attract neutrophils to sites of injury. Cu deficiency was found to have no effect on MIP-2 concentration in the lung. Second, because neutrophils are larger than the smallest blood vessels through which they pass in the lungs, their ability to deform was assessed. Compared to neutrophils from Cu-adequate rats, those from Cu-deficient rats required increased pressure to flow through a filter with pores similar in diameter to small blood vessels. Further, measurement of a structural protein that confers stiffness to cells was found to be greater in Cu-deficient than in Cu-adequate neutrophils. These findings indicate that reduced deformability is a major cause for the enhanced accumulation of neutrophils in Cu-deficient lungs and helps to explain the increased tendency toward inflammation in dietary Cu deficiency.

Technical Abstract: We have previously shown that dietary copper deficiency augments neutrophil accumulation in the lung microvasculature. The current study was designed to determine whether a diet deficient in copper promotes neutrophil chemoattraction within the lung vasculature or if it alters the mechanical properties of the neutrophil thus restricting passage through the microvessels. Sprague-Dawley rats were fed purified diets which were either copper-adequate (6.3 ug Cu/g diet) or copper-deficient (0.3 ug Cu/g diet) for 4 weeks. To assess neutrophil chemoattraction, bronchoalveolar lavage fluid was assayed for the neutrophil chemokine macrophage inflammatory protein-2 (MIP-2) by ELISA. Neutrophil deformability was determined by measuring the pressure required to pass isolated neutrophils through a 5 um polycarbonate filter. The MIP-2 concentration was not significantly different between the dietary groups (Cu-adequate 435.4 ± 11.9 vs Cu-deficient 425.6 ± 14.8 pg/ml). However, more pressure was needed to push Cu-deficient neutrophils through the filter compared to controls (Cu-adequate 0.150 ± 0.032 vs Cu-deficient 0.284 ± 0.037 mmHg/s). Staining of F-actin with FITC-Phalloidan showed greater F-actin polymerization and shape change in the Cu-deficient group. These results suggest that dietary copper deficiency reduces the deformability of neutrophils by promoting F-actin polymerization. Since most neutrophils must deform during passage from arterioles to venules in the lungs, we propose that copper-deficient neutrophils accumulate in the lung because they are less deformable.