title: Activation of the alternative complement pathway by red blood cells from patients with sickle cell disease.
abstract: Increased activation of the alternative pathway of complement in serum from sickle cell disease (SCD) patients has been reported. We now show that this selective activation is not an artifact of clotting by measuring increased plasma concentrations of Bb in sickle cell patients compared to controls. Furthermore, we show that red blood cells (RBC) from SCD patients activate the alternative complement pathway more than control RBC in an in vitro system. RBC were incubated in 50% normal human serum chelated with 3.5 mM MgCl2 and 10 mM EGTA to block activation by the classical pathway, but allow alternative pathway activation. SCD RBC yielded significantly more activation, as measured by an EIA for C3, P complexes, than control RBC. Denser SCD RBC produced more activation than control RBC, unfractionated SCD RBC, and less dense SCD RBC. These findings are consistent with the hypothesis that dense irreversibly sickled cells, or membrane spicules or vesicles derived from them, may result in complement activation.
authors.affiliation: Department of Immunology/Microbiology, Rush Medical College, Chicago, Illinois 60612.
authors.forename: D S
authors.initials: DS
authors.lastname: Chudwin
authors.forename: C
authors.initials: C
authors.lastname: Papierniak
authors.forename: T F
authors.initials: TF
authors.lastname: Lint
authors.forename: A D
authors.initials: AD
authors.lastname: Korenblit
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood* / Q000276:immunology; D002499:Centrifugation, Density Gradient; D003167:Complement Activation / Q000276:immunology*; D051561:Complement C3 Convertase, Alternative Pathway; D003179:Complement C3b / Q000032:analysis / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D003179:Complement C3b; D051561:Complement C3 Convertase, Alternative Pathway