Mechanisms of the anti-inflammatory effects of hydroxyethyl starch demonstrated in a flow-based model of neutrophil recruitment by endothelial cells.
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OBJECTIVE: To determine whether plasma volume expander hydroxyethyl starch (HES) may protect against reperfusion injury through an ability to reduce neutrophil recruitment. DESIGN: An in vitro study using paired comparisons of adhesion of flowing neutrophils. SETTING: A collaboration between clinical and basic science departments in a university hospital. SUBJECTS: Neutrophils and cultured human umbilical vein endothelial cells (HUVEC). INTERVENTIONS: Treatment with HES (average molecular weight of 200 kd and substitution of 0.62) at clinically relevant concentrations or with gelatin solution (average molecular weight of 30 kDa) of comparable viscosity. MEASUREMENTS AND MAIN RESULTS: Glass capillaries were coated internally with either purified adhesion molecules or HUVEC, which were treated with tumor necrosis factor-alpha in the presence or absence of HES. Neutrophils were perfused over these surfaces (with or without HES) and their recruitment quantified by video microscopy. Expression of adhesion molecules and of the chemokine interleukin-8 by HUVEC were analyzed by enzyme-linked immunosorbent assay and quantitation of messenger RNA. HES over a wide range of concentrations had no effect on selectin- or integrin-mediated adhesion of neutrophils. However, when HUVEC were cultured with 1.5% wt/vol HES, neutrophil capture induced by low-dose (1 unit/mL) tumor necrosis factor-alpha and transendothelial migration induced by high-dose (100 units/mL) tumor necrosis factor-alpha were significantly inhibited (p <.05, in each case). The effects were linked with reductions in expression of E-selectin and interleukin-8 by HUVEC at these respective tumor necrosis factor-alpha concentrations (p <.05, in each case). Gelatin (2% wt/vol) had no significant effect in assays with HUVEC. CONCLUSIONS: Application of HES to HUVEC exerts an inhibitory effect on different stages of neutrophil recruitment, depending on the level of the inflammatory stimulus. These effects are associated with reduced adhesion molecule expression and chemokine production. In vivo, comparable effects might protect against complications associated with reperfusion injury.
|Number of pages||7|
|Journal||Critical care medicine|
|Publication status||Published - 1 May 2008|
- endothelial cells, plasma substitutes, reperfusion injury, neutrophils, starch