Intravascular granulocyte aggregates caused by the selectin-binding carbohydrate fucoidin in pig kidneys.
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.
Department of Congenital Heart Disease, German Heart Institute, Berlin, Germany. dittrich@kikli.ukl.uni-freiburg.de
Sven
S
Dittrich
Frank
F
Lippek
Alexander
A
Gratopp
Christian
C
Grosse-Siestrup
Peter E
PE
Lange
Christoph
C
Bührer
D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D011134:Polysaccharides / Q000009:adverse effects* / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D012212:Rheology; D019087:Selectins / Q000378:metabolism*; D013314:Stress, Mechanical; D013552:Swine
D011134:Polysaccharides; D019087:Selectins; C007789:fucoidan