title: Soluble complement receptor 1 inhibits both complement and granulocyte activation during ex vivo hemodialysis.
abstract: Hemodialysis with cellulosic membranes results in both complement and granulocyte activation. We investigated the effects of soluble complement receptor 1 (sCR1), a potent complement inhibitor, on both complement and granulocyte activation in an ex vivo model of dialysis. Measurements were made of complement activation (radioimmunoassay for C3a desArg) as well as granulocyte activation (flow cytometric measurements of reactive oxygen species production, granulocyte CD11b/CD18 (MAC-1) expression and CD62L (L-selectin) expression). sCR1 completely abolished the generation of plasma C3a desArg during ex vivo hemodialysis. Without sCR1, C3a desArg levels rose from 968 +/- 373 ng/ml to 4961 +/- 40 ng/ml by the end of the ex vivo procedure (p < 0.001). sCR1 also completely inhibited MAC-1 upregulation and L-selectin shedding from granulocytes during ex vivo hemodialysis. With sCR1 there was still a statistically significant increase in granulocyte reactive oxygen species production (from 2.42 +/- 0.1 fluorescence channels to 6.47 +/- 0.7 fluorescence channels, p < 0.01) but a 50% inhibition when compared with experiments without sCR1 (3.15 +/- 0.5 to 11.2 +/- 1.9, p < 0.01). We conclude that sCR1 completely abolishes complement activation and changes in granulocyte cell adhesion molecules during ex vivo hemodialysis with cellulosic membranes. sCR1 partially inhibits granulocyte reactive oxygen species formation.
authors.affiliation: Division of Nephrology, Maine Medical Center, Portland 04102, USA.
authors.forename: J
authors.initials: J
authors.lastname: Himmelfarb
authors.forename: E
authors.initials: E
authors.lastname: McMonagle
authors.forename: D
authors.initials: D
authors.lastname: Holbrook
authors.forename: C
authors.initials: C
authors.lastname: Toth
mesh_terms: D000706:Anaphylatoxins / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D003167:Complement Activation; D015926:Complement C3a / Q000031:analogs & derivatives* / Q000032:analysis; D006098:Granulocytes / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D019041:L-Selectin / Q000096:biosynthesis*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis*; D017382:Reactive Oxygen Species; D011951:Receptors, Complement / Q000502:physiology*; D006435:Renal Dialysis
chemical_list: D000706:Anaphylatoxins; D015415:Biomarkers; D016177:Macrophage-1 Antigen; D017382:Reactive Oxygen Species; D011951:Receptors, Complement; C044541:complement C3a, des-Arg-(77)-; D019041:L-Selectin; D015926:Complement C3a