|Schuschke, Dale - UNIVERSITY OF LOUISVILLE|
|Miller, F - UNIVERSITY OF LOUISVILLE|
Submitted to: Immunology Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 14, 2000
Publication Date: March 1, 2001
Citation: Schuschke, D.A., Saari, J.T., Miller, F.N. 2001. Leukocyte-endothelial adhesion is impaired in the cremaster muscle microcirculation of the copper-deficient rat. Immunology Letters. 76:139-144. Interpretive Summary: Various aspects of immune function are altered by dietary copper deficiency. Immune cells (leukocytes) circulating in the blood are reduced in number, their structure is altered and their ability to kill invading bacteria is reduced. The purpose of this study was to examine the effect of dietary copper deficiency on the ability of circulating leukocytes to attach to blood vessel walls, a necessary precursor to their penetration into tissue to attack invading organisms. Initial transient interactions (rolling) and subsequent firm attachments (sticking) of leukocytes to vessel walls are caused by increased production of adhesion molecules in response to tissue inflammation or bacterial invasion. Microscopic observation revealed that the numbers of both rolling and sticking leukocytes on vessel walls in response to inflammatory chemicals were reduced in the circulation of copper-deficient rats. This finding suggests impaired production of adhesion molecules and indicates another mechanism whereby immune response is reduced in copper deficiency.
Technical Abstract: Dietary copper deficiency impairs the function of both the vascular endothelium and circulating leukocytes. In the current study, leukocyte- endothelium adhesion was observed in the in vivo cremaster muscle microcirculation of copper-adequate and copper-deficient rats. Male, weanling Sprague-Dawley rats were fed purified diets that were either adequate (5.6 ug/g) or deficient (0.3 ug/g) in copper. Adhesion was stimulated with the inflammatory mediators TNF-alpha and bradykinin and the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). Intravascular adhesion of leukocytes to the vascular endothelium was significantly attenuated in the copper-deficient group in response to all three agonists. These results occurred without any difference in intravascular wall shear rate between the dietary groups. Based on previous work, we propose that the attenuated response is caused by either decreased expression of adhesion molecules on leukocytes and endothelial cells or by inhibition of the endothelial cell calcium signaling associated with copper deficiency.