A major role for CD62P/CD15s interaction in leukocyte margination during hemodialysis

Abstract

We investigated expression of several antigens on neutrophils and monocytes, involved in cell adhesion, from patients hemodialyzed with cellulosic and polyacrylonitrile membranes. Among the antigens tested only the expression of CD15s and CD11b was significantly increased on neutrophils and monocytes in patients dialyzed with cellulosic membranes. No changes occurred with polyacrylonitrile membranes. Leukocyte counts from patients dialyzed with cuprophane membranes decreased at the same time as expression of cellular CD15s increased, resulting in a significant negative correlation at all time points tested. No correlation was found between the drop of monocytes and their expression of CD11b. When CD15s expression increased on neutrophils and monocytes, we observed a concomitant increase of CD62P, a specific selectin of activated platelets. When whole blood cells were incubated with complement activated serum both antigens increased but not when cells were incubated with hrC5a. We also observed that CD61, a platelet phenotypic antigen, was present on leukocytes incubated with complement activated serum. At the time when platelet-leukocyte coaggregates decreased, CD62P expression remained stable on leukocytes, suggesting that both neutrophils and monocytes are able to trap either CD62P shed by activated platelets or soluble CD62P present in normal human serum. The present study documents a major role of P-selectin (CD62P)/sialyl-Lewis x (CD15s) interaction in the transient leukocyte margination during hemodialysis.

Hemodialysis-Related Bioincompatibility and Adhesion Molecules

“…CD11c/CD18 (CR4, p150/95), another member of the leukocyte integrin family, also showed an upregulation during dialysis with unmodified cellulose membranes (13,15,16); however this phenomenon was not confirmed by Stuard et al (10). The expression of CD11a/CD18 (LFA-1, leukocyte function antigen-1) with whatever membrane did not change during dialysis, (8, 10,11,13,15).…”

“…No (10,13,14) or only minor (11) upregulation was observed during dialysis with polyacrylonitrile and polyamide membranes. A correlation between the upregulation of CD11b across the dialyzer at the fifth minute of dialysis and the decrease in granulocyte count was found (12).…”

Platelet-Leukocyte Interactions in Hemodialysis Patients: Culprit or Bystander?

“…The property which causes monocytes to preferentially bind platelets, a possible basis for the involvement of activated platelets in atherosclerosis (67), is at presently unknown. It has been conjectured that a different conformation ofadhesive molecules orithe monocyte surface allow a better interaction with activated platelets, and/or some additional binding mechanism may be involved (38,45). The latter might be represented by CD40-CD40 ligand interactions.…”

“…One study (38) reported that in patients chronically dialyzed with cuprophan membrane, almost all monocytes (80 to 95%) express pre-dialysis levels of CD62P (a marker of platelet-monocyte aggregation). Levels ofplatelet-monocyte conjugates can further increase during the hemodialysis procedure when using dialyzer membrane materials like cuprophan (38,40), cellulose diacetate (41,43), polysulphone (37) and polymethylmethacrylate (41).…”

“…One study (38) reported that in patients chronically dialyzed with cuprophan membrane, almost all monocytes (80 to 95%) express pre-dialysis levels of CD62P (a marker of platelet-monocyte aggregation). Levels ofplatelet-monocyte conjugates can further increase during the hemodialysis procedure when using dialyzer membrane materials like cuprophan (38,40), cellulose diacetate (41,43), polysulphone (37) and polymethylmethacrylate (41). However, use of several other membranes including ethylenevinylalcohol (EVAL) and polyacrylonytrile (42), benzyl cellulose and hemophan (40), and PEG acid grafted cellulose (41) is not associated with any significant increase in platelet-monocyte aggregation during dialysis, making them better choices for hemodialysis.…”