Modulation of adhesion molecules on leukocytes during clinical and experimental hemodialysis : endothelial cell interacions

In patients on hemodialysis the sequential steps required for adhesion molecule mediated adherence of leukocytes to endothelial cells are unphysiologically disrupted since cell activation with subsequent alterations in adhesion molecule phenotypes takes place in the extracorporeal circuit far away from the respective endothelial cell ligand. The aims of the present investigations were to study the changes in adhesion molecule phenotypes on inflammatory cells induced by clinical and experimental hemodialysis and the consequences with regard to the capacity of the cells to adhere to endothelial cells.

We analysed the generation of complement products, the importance of the alternative and the classical pathways of the complement system, production of interleukin-1 and the phenotypic changes in adhesion molecules on leukocytes during and after hemodialysis. Clinical and experimental cuprophan hemodialysis resulted in a rapid and pronounced decrease in the expression of CD62L on granulocytes and a concomitant marked increase in the expression of CDllb/CD18. By contrast, the CD62L expression on monocytes increased during clinical cuprophan hemodialysis and the upregulation of CD11b/CD18 occurred much slower. An early increase in the expression of CD11b/CD18 on monocytes was accompanied by an increase by plasma interleukin lbeta later during dialysis.

During clinical and experimental polysulfone hemodialysis the changes in adhesion molecule phenotypes were much less pronounced than when dialyses were performed with cuprophan membranes. In vitro experiments showed that both the alternative and the classical pathways of the complement system are involved in the generation of factors with the ability to mobilize adhesion molecules on inflammatory cells. Analyses of adhesion molecule phenotypes after hemodialysis showed that significant alterations persist several hours after termination of treatment. The responsiveness to chemotactic stimuli is impaired post-dialysis both in comparison to predialysis and to the responsiveness of cells obtained from healthy subjects. These studies emphasize the importance of including the interdialytic period in the evaluation of the influence of hemodialysis on the behaviour of inflammatory cells.

We also analysed the ability of leukocytes obtained before and during hemodialysis to adhere to human adult endothelial cells. Granulocytes collected at the end of cuprophan hemodialysis had an impaired ability to adhere to endothelial cells as compared to cells obtained pre-dialysis. Serum factors with the ability to inhibit monocyte and granulocyte adherence to endothelial cells seem to be generated or accumulated during cuprophan hemodialysis. The findings in the present investigations contribute to an increased understanding of the factors involved in the impaired immune response observed in patients on maintenance hemodialysis.