Modulation of granulocyte LAM-1 and MAC-1 during dialysis--a prospective, randomized controlled trial

Hemodialysis with first-use cellulosic dialysis membranes results in activation of the alternative pathway of complement and profound neutropenia followed by rebound leukocytosis. The neutropenia has been shown to be associated with increased expression of adhesion receptors and pulmonary sequestration of granulocytes. However, the mechanism underlying the return of the granulocytes has not been elucidated. We determined simultaneously the changes in the granulocyte adhesion receptor MAC-1 (CD11b-CD18) and the selectin LAM-1 receptor during dialysis using a complement activating and a non-complement activating membrane, in a randomized, cross-over study. With initiation of dialysis with cellulosic membranes, there was a rapid and prominent increase in the expression of MAC-1 receptors. At the nadir of granulocyte count, 15 minutes after initiation of dialysis with the complement activating membrane, there was a four-fold increase in the MAC-1 receptor expression. At the same time, there was a two-fold decrease in LAM-1 expression. There were no changes in the expression of two other granulocyte receptors CD11a and CD15 which are known not to be modulated during granulocyte activation. Granulocytes harvested during dialysis and which had high MAC-1 and low LAM-1 expression had a significantly decreased adherence to endothelial cell monolayers. Dialysis of the same patients with non-complement activating membranes resulted in no significant change in the expression of these receptors on granulocytes nor in their adherence to endothelial cells. These results shed new light on the mechanism of the cyclical granulocytopenia and rebound granulocytosis during dialysis with new cellulosic membranes.