Isolation and characterization of complement receptors CR1 from human peripheral nerves.
Extracts from myelinated and unmyelinated nerves, prepared using Nonidet P-40, contained receptors for C3b/C4b (CR1). Extracts from myelinated nerves inhibited EAC3b rosette formation with peripheral blood leucocytes and agglutinated EAC3b, whereas extract from unmyelinated nerves did not. Rosette formation with EAC3bi or EAC3d was not affected. CR1 in extracts from myelinated nerves also expressed decay-accelerating activity of the alternative pathway C3 convertase and cofactor activity in factor I-mediated cleavage of C3b, whereas CR1 in extract from unmyelinated nerves did not. Monoclonal anti-CR1 antibodies, but not monoclonal anti-CR2 (C3d receptors) or anti-CR3 (C3bi receptors) antibodies inhibited the functional activities. Accordingly, CR1 are the only C3 receptor present in the extracts and only CR1 in myelinated nerve extracts are functionally active. CR1 in both myelinated and unmyelinated nerve extracts had a molecular weight of approximately 190 kDa. The electrophoretic mobility did not change after reduction and the 190 kDa band was stained by concanavalin A, indicating that the CR1 are single-chained glycoproteins. Binding to lentil lectin-Sepharose 4B further sustained the glycoprotein nature of the CR1. Periodic acid abolished functional activities of CR1, whereas trypsin and heat did not, indicating the functional significance of the carbohydrate moiety. That CR1 are functionally active in myelinated nerves, but not in unmyelinated nerves, may therefore be due to differences in the carbohydrate moiety. The cofactor and decay-accelerating activities of CR1 may be of significance in the pathogenesis of demyelinating polyneuropathies by limiting complement activation.
Vedeler
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Broegelmann Research Laboratory for Microbiology, Haukeland Hospital, Bergen, Norway.
Matre
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Fischer
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D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002846:Chromatography, Affinity; D006801:Humans; D009186:Myelin Sheath / Q000032:analysis; D010525:Peripheral Nerves / Q000032:analysis*; D011951:Receptors, Complement / Q000302:isolation & purification* / Q000378:metabolism; D017463:Receptors, Complement 3b; D012397:Rosette Formation
D000911:Antibodies, Monoclonal; D011951:Receptors, Complement; D017463:Receptors, Complement 3b