
<ArticleTitle>Effect of <prot>aprotinin</prot> on endothelial cell activation.</ArticleTitle>
<AbstractText>BACKGROUND: Cardiopulmonary bypass surgery is often accompanied by a systemic inflammatory response, which can lead to postoperative complications in high-risk patients. This is mediated in part through a systemic rise in inflammatory cytokine levels and the sequestration of leukocytes within organs. <prot>Aprotinin</prot> has previously been shown to exert an anti-inflammatory effect by preventing the capacity of leukocytes to transmigrate through vascular endothelium. Here we have focused on whether <prot>aprotinin</prot> has an effect on endothelial cell activation and adhesion molecule expression in response to <prot>tumor necrosis factor-alpha</prot>, particularly with reference to whether <prot>aprotinin</prot> inhibits tumor necrosis factor-stimulated neutrophil transendothelial migration.Methods and Results: <prot>Intercellular adhesion molecule-1</prot>, <prot>vascular cell adhesion molecule-1</prot>, and <prot>E-selectin</prot> expression was studied in <prot>tumor necrosis factor-alpha</prot>-activated human umbilical vein endothelial cells in the presence of <prot>aprotinin</prot> at 200, 800, and 1600 kIU/mL. <prot>Aprotinin</prot> inhibited <prot>tumor necrosis factor-alpha</prot>-stimulated expression of <prot>intercellular adhesion molecule-1</prot> (P =.019 at 1600 kIU/mL) and <prot>vascular cell adhesion molecule-1</prot> (P =.003 at 1600 kIU/mL) but not <prot>E-selectin</prot>. Similar results were obtained in the dermal microvascular endothelial cell line, HMEC-1, which exhibited diminished <prot>intercellular adhesion molecule-1</prot> expression in the presence of <prot>aprotinin</prot> (P =.040 at 800 kIU/mL and P &#60;.001 at 1600 kIU/mL). <prot>Aprotinin</prot> also significantly inhibited neutrophil transmigration across <prot>tumor necrosis factor-alpha</prot>-activated human umbilical vein endothelial cells (P =.046 at 1600 kIU/mL). CONCLUSIONS: We have demonstrated that <prot>aprotinin</prot> inhibits <prot>intercellular adhesion molecule-1</prot> and <prot>vascular cell adhesion molecule-1</prot>, but not <prot>E-selectin</prot>, expression on <prot>tumor necrosis factor-alpha</prot>-activated endothelial cells and that transendothelial migration by neutrophils is also specifically suppressed under these conditions. Our results indicate that endothelial cells can be specifically targeted by <prot>aprotinin</prot>, therefore adding to our understanding of the anti-inflammatory mechanism of action of <prot>aprotinin</prot> during cardiopulmonary bypass.</AbstractText>
