(Circulation. 2000;102:1420.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Functional Protection by Acute Phase Proteins 
1-Acid Glycoprotein and 1-Antitrypsin Against Ischemia/Reperfusion Injury by Preventing Apoptosis and Inflammation
From the Department of General Surgery (M.A.R.C.D., V.H.H., C.v.V., T.G.A.M.W., W.A.B.), University of Maastricht, Maastricht, the Netherlands, and the Department of Molecular Biology (G.D., P.V.), Flanders Interuniversity Institute for Biotechnology and University of Ghent, Ghent, Belgium.
Background—Ischemia
followed by reperfusion (I/R) causes apoptosis, inflammation,
and tissue damage leading to organ malfunction. Ischemic
preconditioning can protect against such injury. This study
investigates the contribution of the acute phase proteins
1-acid glycoprotein (AGP) and
1-antitrypsin (AAT) to the protective effect of
ischemic preconditioning in the kidney.
Methods and Results—Exogenous AGP and AAT inhibited
apoptosis and inflammation after 45 minutes of renal I/R in a
murine model. AGP and AAT administered at reperfusion prevented
apoptosis at 2 hours and 24 hours, as evaluated by the presence
of internucleosomal DNA cleavage, terminal
deoxynucleotidyl transferase–mediated dUTP nick
end-labeling, and the determination of renal caspase-1– and
caspase-3–like activity. AGP and AAT exerted anti-inflammatory
effects, as reflected by reduced renal tumor necrosis factor-
expression and neutrophil influx after 24 hours. In general, these
agents improved renal function. Similar effects were observed when AGP
and AAT were administered 2 hours after reperfusion but to a lesser
extent and without functional improvement. Moreover, I/R elicited an
acute phase response, as reflected by elevated serum AGP and serum
amyloid P (SAP) levels after 24 hours, and increased hepatic acute
phase protein mRNA levels after 18 hours of renal reperfusion.
Conclusions—We propose that the antiapoptotic and anti-inflammatory effects of AGP and AAT contribute to the delayed type of protection associated with ischemic preconditioning and other insults. This mechanism is potentially involved in the course of many clinical conditions associated with I/R injury. Moreover, exogenous administration of these proteins may provide new therapeutic means of treatment.
Key Words: ischemia • reperfusion • kidney • immune system • apoptosis
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