Hydroxyethyl Starch Inhibits Neutrophil Adhesion and Transendothelial Migration

Abstract

A resuscitation strategy that significantly alters the state of neutrophil (PMN) activation may impact organ function and survivability after shock. Various resuscitative fluids have been shown to elicit a severe immune activation and an upregulation of cellular injury markers, whereas other fluids have been shown to be protective. Recent studies have demonstrated that hydroxyethyl starch (HES), an artificial colloid, may exert significant anti-inflammatory effects, whereas conflicting studies with the same substance have shown an increase in PMN activation. Successful manipulation of the early immune events associated with hemorrhage and resuscitation will require a better understanding of the possible pro- or anti-inflammatory effects of resuscitation fluids. Our study investigated the effect of HES directly on PMN and cultured vascular endothelial cells in vitro. The effect of HES on PMN surface expression of CD11b and L-selectin was measured by flow cytometry. PMN activation response to HES was measured using a shape-change assay in response to formyl-methionyl-leucyl-phenylalanine (f-MLP). The effect of HES on endothelial cell surface expression of E-selectin, P-selectin, vascular cell adhesion molecule-1(VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) was evaluated by enzyme-linked immunoabsorbant assay. PMN rolling, adhesion, and migration events were measured using direct microscopy under conditions simulating microvascular flow. PMN surface expression of CD11b and L-selectin in whole blood samples and isolated PMNs were unaffected by exposure to HES. HES had no effect on the normal f-MLP dose-dependent increase in PMN activation. In the absence of IL-1 stimulation, there was a small but statistically significant (P < 0.05) increase in ICAM-1 after exposure to HES. After stimulation with IL-1 (10 U/mL), HES had no effect on the expression of P-selectin, E-selectin, ICAM-1, or VCAM-1. Under simulated microvascular flow conditions in vitro, HES significantly diminished the PMN tethering rate (P < 0.05) and the transendothelial migration rate (P < 0.05) in a dose-dependent manner. HES significantly alters the function of the PMN at the interface of the PMN responding to activated endothelium. The effect occurs, surprisingly, without a coincident effect on the state of PMN activation or a significant change in the surface expression of the adhesion molecules responsible for PMN-endothelial interaction.

Effect of High- and Low-molecular-weight Low-substituted Hydroxyethyl Starch on Blood Coagulation during Acute Normovolemic Hemodilution in Pigs

“…In addition, investigation of adverse side effects (i.e., impairment of blood coagulation) of high-and low-molecular-weight low-substituted HES solutions in further clinical settings (acute vs. chronic vs. repetitive administration) are desirable to evaluate their clinical utility. Besides the extensively described volume restoring properties, HES seems to exert significant beneficial antiinflammatory effects, 34,35 such as a diminishment of polymorphonuclear neutrophil sequestration in multiple organs. 34,36 Recent studies have shown that the clinically relevant effect of HES on leukocyte sequestration depends on the regulation of the integrin function.…”

“…Besides the extensively described volume restoring properties, HES seems to exert significant beneficial antiinflammatory effects, 34,35 such as a diminishment of polymorphonuclear neutrophil sequestration in multiple organs. 34,36 Recent studies have shown that the clinically relevant effect of HES on leukocyte sequestration depends on the regulation of the integrin function. 36 The duration of the antiinflammatory effect after HES administration thus may be largely determined by the intravascular elimination of the colloid.…”

L’hydroxyéthylamidon 130/0,4 atténue les dommages hépatiques précoces causés par les lésions d’ischémie/reperfusion

“…[14][15][16][17][18][24][25][26][27][28][29] We shared the commonly held perception that both volume effect and molecule characteristics are among the most important factors in organ protection; however, the current study demonstrated that the HES molecule plays a role in hepatoprotection against reperfusion injury. The infused volume of HES solution (13 mLÁkg -1 ) adjusted to the weight of the rats was within the doses reported for volume repletion in clinical studies.…”

“…[7][8][9][10][11][12][13] Best known for their use as intravascular volume expanders, HES solutions are also associated with microcirculatory improvement and antiinflammatory properties. [14][15][16][17][18] Despite their adverse effects in other settings, namely, on renal function, coagulation, and tissue storage, it was suggested previously that the older high molecular weight HES can reduce the deleterious effect of IRI. 14,19 Distinct types of HES show clear differences in pharmacokinetic, clinical efficacy, and adverse effects.…”

Extracorporeal perfusion of isolated organs of large animals – Bridging the gap between in vitro and in vivo studies

“…While mannitol is considered an inert substance, recent research has suggested possible interdependencies with monocyte and neutrophil function (upregulation of HLA-DR in monocytes, upregulation of CD11b in neutrophils and monocytes, and inhibition of neutrophil apoptosis (Turina et al, 2008)). Hydroxyethyl starch (Handrigan et al, 2005;Matharu et al, 2008) and cellulose (Hänsch et al, 1996;Moore et al, 2001;Bae et al, 2004;Ewoldt et al, 2004;Hernández et al, 2004Hernández et al, , 2009 have also both been shown to alter inflammatory responses due to their different effects on neutrophils. While glucose is also able to support the maintenance of oncotic pressure (Hicks et al, 2006), it supports the specimen's metabolism and survival.…”