Proinflammatory effects of copper deficiency on neutrophils and lung endothelial cells.
Dietary copper deficiency increases the accumulation of circulating neutrophils in the rat lung microcirculation. This process includes neutrophil adhesion to, migration along, and emigration though the vascular endothelium. The current study was designed to examine the role of copper in each of these steps. Neutrophils were isolated from rats fed either a copper-adequate (CuA, 6.1 microg Cu/g diet) or copper-deficient diet (CuD, 0.3 microg Cu/g diet) for 4 weeks. First, transient and firm adhesion of neutrophils to P-selectin 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 signalling pathway. Third, the contractile mechanism of endothelial cells was studied. Elevated F-actin formation in Cu-chelated lung microvascular endothelial cells suggests that neutrophil emigration 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.
Lominadze
David
D
Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40292, USA.
Saari
Jack T
JT
Percival
Susan S
SS
Schuschke
Dale A
DA
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D003300:Copper / Q000172:deficiency*; D003599:Cytoskeleton / Q000502:physiology; D004032:Diet; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000166:cytology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D039481:CD11b Antigen; D018821:CD18 Antigens; D016209:Interleukin-8; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003300:Copper