Increased expression of an adhesion-promoting surface glycoprotein in the granulocytopenia of hemodialysis.
To identify the mechanisms accounting for hemodialysis-induced granulocytopenia, we undertook quantitative kinetic studies of a granulocyte-adhesion-promoting surface glycoprotein (Mo1). In eight patients undergoing maintenance hemodialysis, there was a fivefold increase in the mean cell-surface expression of Mo1 within 15 minutes after the start of dialysis with a new cuprophane membrane. The peak increase in surface Mo1 coincided with the maximal drop in neutrophil count and with the peak rise in the plasma levels of the complement-activation products C5a desArg and C3a desArg. During dialysis on a membrane being reused for the fifth time, no significant complement activation, no increase in Mo1 expression, and no change in neutrophil count were seen. C5a desArg (but not C3a desArg) induced a comparable increase in Mo1 expression on normal granulocytes in vitro at concentrations similar to those measured in vivo. Chemotactic peptide-induced granulocyte aggregation (a reflection of increased cell-to-cell adhesiveness) was specifically blocked by mouse monoclonal antibodies to Mo1 in vitro. These data suggest that the increased expression of Mo1 on granulocytes in vivo is in part mediated by C5a (and C5a desArg). The quantitative increase in granulocyte-surface Mo1 may provide a mechanism for initiating leukoaggregation, sequestration of granulocytes, and neutropenia during hemodialysis.
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000097:blood / Q000209:etiology*; D001798:Blood Proteins / Q000032:analysis*; D002448:Cell Adhesion; D003176:Complement C3 / Q000032:analysis; D015926:Complement C3a; D003182:Complement C5 / Q000032:analysis; D015936:Complement C5a; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006098:Granulocytes / Q000032:analysis; D006801:Humans; D007688:Kidneys, Artificial / Q000009:adverse effects; D007958:Leukocyte Count; D016177:Macrophage-1 Antigen; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*
D001798:Blood Proteins; D003176:Complement C3; D003182:Complement C5; D006023:Glycoproteins; D016177:Macrophage-1 Antigen; D015926:Complement C3a; D015936:Complement C5a