Ceruloplasmin reduces the adhesion and scavenges superoxide during the interaction of activated polymorphonuclear leukocytes with endothelial cells.
The plasma protein, ceruloplasmin, has been implicated as an anti-inflammatory agent, although this property has not been demonstrated unequivocally in vivo. The role of this protein in an in vitro system of cultured endothelial cells and polymorphonuclear leukocytes (PMNs) was investigated. One of the initial steps in an inflammatory response is increased adhesion between PMNs and the endothelial lining of the blood vessels. The results showed that ceruloplasmin interferes with this process and reduces the number of phorbol myristate acetate-activated leukocytes that adhere to endothelium. Preincubation of either the activated PMNs or the endothelium with ceruloplasmin did not produce the same results, suggesting that the continuous presence of ceruloplasmin is required. During attachment PMNs become activated and release a variety of substances, including toxic oxygen species such as superoxide and hydrogen peroxide. In the in vitro system used in this study no injury occurred to the endothelial cells, as measured by 51Cr release, when activated PMNs were added with ceruloplasmin. The data show that ceruloplasmin reduced, in a dose dependent manner, the levels of superoxide produced by the activated PMNs, further supporting ceruloplasmin's previously reported role as a scavenger of superoxide. Ceruloplasmin also reduced the levels of superoxide when activated PMNs were in contact with endothelial cells. Although ceruloplasmin interfered with the copper-dependent scavenger enzyme, superoxide dismutase (SOD), in a cell-free system, ceruloplasmin had no effect on SOD in intact endothelial cells. These results suggest that ceruloplasmin may act as an anti-inflammatory agent by reducing the number of PMNs attaching to endothelium and by acting as an extracellular scavenger of superoxide.
Broadley
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Pathology Department, Vanderbilt University, Nashville, Tennessee 37232.
Hoover
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RL
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002570:Ceruloplasmin / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D002570:Ceruloplasmin