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Nephrol Dial Transplant (2003) 18: 2589-2595
© 2003 European Renal Association-European Dialysis and Transplant Association


Original Article

Haemodialysis-induced pulmonary granulocyte sequestration in rabbits is organ specific

Marco E. van Teijlingen1, Menso J. Nubé2, Piet M. ter Wee2, Michiel H. van Wijhe1, Piet Borgdorff1 and Geert-Jan Tangelder1

1Laboratory for Physiology and 2Department of Nephrology, Institute for Cardiovascular Research, VU—University Medical Center, Amsterdam, The Netherlands

Correspondence and offprint requests to: Marco E. van Teijlingen, Laboratory for Physiology, Institute for Cardiovascular Research (ICaR-VU), VU—University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Email: teijlingen{at}physiol.med.vu.nl

Background. Haemodialysis (HD) with cuprophan (CU) dialysers leads to a severe transient granulocytopenia. In the present study, we challenge the hypothesis that granulocytes sequester within the pulmonary vasculature simply because this is the first vascular bed encountered. This hypothesis is based upon experiments in which activated plasma or complement fragments were infused into animals, and may not pertain to the more complex HD situation.

Methods. We used a rabbit model of HD, and returned the blood into the caval vein (v-HD) or aorta (a-HD). The mesentery was continuously monitored by intravital video microscopy, whereas other tissues were collected at the nadir of granulocytopenia and analysed immunohistochemically.

Results. Compared with controls, the number of granulocytes within alveolar walls was almost 2-fold higher following HD, with no difference between venous and arterial blood return. In addition, both v-HD and a-HD induced granulocyte accumulation within part of the larger pulmonary microvessels, though the amount of granulocytes found was 2-fold higher after v-HD. At no time did a-HD induce granulocyte sequestration within the mesenteric microcirculation. Neither did arterial return increase their number in other first-pass tissues like skeletal muscle or renal glomeruli, but it did so in the liver. In the heart, granulocyte content decreased during HD.

Conclusions. Pulmonary sequestration of granulocytes during CU HD is not simply a first-pass effect, but is organ specific to a great extent. The accumulation within larger microvessels suggests an important role for adhesion molecules, whereas cellular stiffening may be involved in granulocyte retention within alveolar capillaries.

Keywords: animal; heart; immunohistochemistry; intravital video microscopy; leukopenia; lungs


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