Background: Cardiopulmonary bypass surgery is often accompanied by a system
ic inflammatory response, which can lead to postoperative complications in
high-risk patients. This is mediated in part through a systemic rise in inf
lammatory cytokine levels and the sequestration of leukocytes within organs
. Aprotinin has previously been shown to exert an anti-inflammatory effect
by preventing the capacity of leukocytes to transmigrate through vascular e
ndothelium. Here we have focused on whether aprotinin has an effect on endo
thelial cell activation and adhesion molecule expression in response to tum
or necrosis factor-alpha, particularly with reference to whether aprotinin
inhibits tumor necrosis factor-stimulated neutrophil transendothelial migra
tion.
Methods and Results: Intercellular adhesion molecule-1, vascular cell adhes
ion molecule-1, and E-selectin expression was studied in tumor necrosis fac
tor-cl-activated human umbilical vein endothelial cells in the presence of
aprotinin at 200, 800, and 1600 kIU/mL. Aprotinin inhibited tumor necrosis
factor-a-stimulated expression of intercellular adhesion molecule-1 (P = .0
19 at 1600 kIU/mL) and vascular cell adhesion molecule-1 (P = .003 at 1600
kIU/mL) but not E-selectin. Similar results were obtained in the dermal mic
rovascular endothelial cell line, HMEC-1, which exhibited diminished interc
ellular adhesion molecule-1 expression in the presence of aprotinin (P = .0
40 at 800 kIU/mL, and P < .001 at 1600 kIU/mL). Aprotinin also significantl
y inhibited neutrophil transmigration across tumor necrosis factor-alpha -a
ctivated human umbilical vein endothelial cells (P = .046 at 1600 kIU/mL).
Conclusions: We have demonstrated that aprotinin inhibits intercellular adh
esion molecule-1 and vascular cell adhesion molecule-1, but not E-selectin,
expression on tumor necrosis factor-alpha -activated endothelial cells and
that transendothelial migration by neutrophils is also specifically suppre
ssed under these conditions. Our results indicate that endothelial cells ca
n be specifically targeted by aprotinin, therefore adding to our understand
ing of the anti-inflammatory mechanism of action of aprotinin during cardio
pulmonary bypass.