Intravascular granulocyte aggregates caused by the selectin‐binding carbohydrate fucoidin in pig kidneys

Abstract

1. Renal postischaemic reperfusion injury constitutes a significant problem after kidney transplantation. The polysaccharide fucoidin improves postischaemic function in lamb hearts, presumably by blocking selectin-mediated leucocyte adhesion. 2. In the present study, eight pairs of ischaemic pig kidneys were reperfused in an ex vivo model with autologous blood with or without fucoidin (100 mg/L). 3. Fucoidin resulted in a significant decrease in renal blood flow (45 +/- 5 vs 178 +/- 22 mL/min per 100 g; P < 0.001) and increased vascular resistance (3.80 +/- 0.07 vs 0.60 +/- 0.12 mmHg/mL per min per 100 g; P < 0.001). 4. Histological examination revealed granulocyte emboli in afferent glomerular arteries in five of six fucoidin-treated kidneys and in one of six controls (Fisher's exact test; P < 0.001). 5. In vitro experiments with human granulocytes showed that large granulocyte aggregates were induced by fucoidin at concentrations similar to those used in reperfused kidneys, whereas slightly lower doses of fucoidin prevented l-selectin-dependent homotypic granulocyte adhesion. 6. The formation of embolizing granulocyte aggregates defines a narrow therapeutic range for fucoidin and calls into question its experimental use as an inhibitor of selectin-mediated leucocyte adhesion.

The Potential Use of Fucoidans from Brown Seaweed as a Dietary Supplement

“…Histological examination revealed granulocyte emboli in afferent glomerular arteries in five of six fucoidan-treated kidneys and in one of six controls. Previous in vitro studies indicated that higher concentrations of fucoidan, similar to that used in this experiment, large granulocyte aggregates were induced by fucoidan, whereas slightly lower doses of fucoidan prevented l-selectin-dependent homotypic granulocyte adhesion [39]. Ischemia was induced in the cremaster (striated) muscle of mice by occluding the main feeding arteriole for 30 minutes [40].…”

The effect of fucoidin on kidney and lung injury in a rat infrarenal aortic ischemia-reperfusion model

“…There are also studies opposed to the protective effect of fucoidin on kidney. Dittrich et al 27 have demonstrated that neutrophil aggregates in the blood caused embolism in renal efferent glomeruli in vitro circulated pig kidneys. However, they claimed that this condition is dose dependent and neutrophil adhesion related to L-selectin decreased when lower doses of fucoidin were administered.…”

Influence of Cold Storage on Renal Ischemia Reperfusion Injury after Non-Heart-Beating Donor Explantation

“…Isolated kidney perfusion was performed in an ex vivo model with normothermic autologous blood [8, 9, 10]. Kidneys were obtained either from anesthetized pigs after clamping the renal vessels in the laboratory or from pigs sacrificed at the slaughterhouse.…”