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Intravascular granulocyte aggregates caused by the selectin‐binding carbohydrate fucoidin in pig kidneys
Author(s) -
Dittrich Sven,
Lippek Frank,
Gratopp Alexander,
GrosseSiestrup Christian,
Lange Peter E,
Bührer Christoph
Publication year - 2002
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2002.03749.x
Subject(s) - granulocyte , selectin , kidney , adhesion , medicine , in vitro , chemistry , inflammation , biochemistry , organic chemistry
Summary 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.