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

Abstract: Modulation of adhesion molecules on leukocytes during clinical and experimental hemodialysis - endothelial cell interactions Pia ThylenIn patients on hemodialysis the sequential steps required for adhesion molecule mediated ad-herence of leukocytes to endothelial cells are unphysiologically disrupted since cell activationwith subsequent alterations in adhesion molecule phenotypes takes place in the extracorporealcircuit far away from the respective endothelial cell ligand.The aims of the present investigations were to study the changes in adhesion molecule phenotypeson inflammatory cells induced by clinical and experimental hemodialysis and the consequenceswith regard to the capacity of the cells to adhere to endothelial cells. We analysed the generationof complement products, the importance of the alternative and the classical pathways of thecomplement system, production of interleukin-1 and the phenotypic changes in adhesion mole-cules on leukocytes during and after hemodialysis. Clinical and experimental cuprophanhemodialysis resulted in a rapid and pronounced decrease in the expression of CD62L on granu-locytes and a concomitant marked increase in the expression of CDllb/CD18. By contrast, theCD62L expression on monocytes increased during clinical cuprophan hemodialysis and the up-regulation 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 duringdialysis. During clinical and experimental polysulfone hemodialysis the changes in adhesionmolecule phenotypes were much less pronounced than when dialyses were performed with cup-rophan membranes. In vitro experiments showed that both the alternative and the classical path-ways of the complement system are involved in the generation of factors with the ability tomobilize adhesion molecules on inflammatory cells. Analyses of adhesion molecule phenotypesafter hemodialysis showed that significant alterations persist several hours after termination oftreatment. The responsiveness to chemotactic stimuli is impaired post-dialysis both in comparisonto pre-dialysis and to the responsiveness of cells obtained from healthy subjects. These studiesemphasize the importance of including the inter-dialytic period in the evaluation of the influenceof hemodialysis on the behaviour of inflammatory cells. We also analysed the ability of leukocytesobtained before and during hemodialysis to adhere to human adult endothelial cells. Granulocytescollected at the end of cuprophan hemodialysis had an impaired ability to adhere to endothelialcells as compared to cells obtained pre-dialysis. Serum factors with the ability to inhibit monocyteand granulocyte adherence to endothelial cells seem to be generated or accumulated duringcuprophan hemodialysis. The findings in the present investigations contribute to an increasedunderstanding of the factors involved in the impaired immune response observed in patients onmaintenance hemodialysis.Key words: Adhesion, adhesion molecules, complement, endothelial cells, hemodialysis, integrins,interleukin, leukocytes, selectins.ISBN: 91-628-2008-7 Stockholm, 1996