Impaired deformability of copper-deficient neutrophils.
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 that were either copper adequate (6.3 microg Cu/g diet) or copper deficient (0.3 microg 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 enzyme-linked immunosorbent assay. Neutrophil deformability was determined by measuring the pressure required to pass isolated neutrophils through a 5-microm polycarbonate filter. The MIP-2 concentration was not significantly different between the dietary groups (Cu adequate, 435.4 +/- 11.9 pg/ml; Cu deficient, 425.6 +/- 14.8 pg/ml). However, compared with controls, more pressure was needed to push Cu-deficient neutrophils through the filter (Cu adequate, 0.150 +/- 0.032 mm Hg/sec; Cu deficient, 0.284 +/- 0.037 mm Hg/sec). Staining of the filamentous actin (F-actin) with FITC-Phalloidin 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. Because 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.
Gordon
Sharon A
SA
Department of Physiology and Biophysics, Health Sciences Center A1115, University of Louisville, Louisville, KY 40292, USA.
Lominadze
David
D
Saari
Jack T
JT
Lentsch
Alex B
AB
Schuschke
Dale A
DA
D000199:Actins / Q000097:blood; D000818:Animals; D003300:Copper / Q000172:deficiency*; D003677:Deficiency Diseases / Q000097:blood*; D004195:Disease Models, Animal; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D003300:Copper