Haemodialysis-induced pulmonary granulocyte sequestration in rabbits is organ specific.
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.
van Teijlingen
Marco E
ME
Laboratory for Physiology, Institute for Cardiovascular Research, VU-University Medical Center, van der Borchorststraat 7, 1081 BT Amsterdam, The Netherlands. teijlingen@physiol.med.vu.nl
Nubé
Menso J
MJ
ter Wee
Piet M
PM
van Wijhe
Michiel H
MH
Borgdorff
Piet
P
Tangelder
Geert-Jan
GJ
D000380:Agranulocytosis / Q000209:etiology / Q000276:immunology*; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology; D023421:Models, Animal; D011817:Rabbits; D006435:Renal Dialysis / Q000009:adverse effects*