title: The interaction of soluble human complement receptor type 1 (sCR1, BRL55730) with human complement component C4.
abstract: Human CR1 is a membrane-bound protein which plays an important role in the control of the human complement system. In addition to its involvement in the processing and clearance of immune complexes with C3b or C4b on their surface, CR1 acts as a cofactor for the proteolysis of C3b and C4b by Factor I. sCR1 is a recombinant, soluble form of CR1 which retains the cofactor activities of CR1, and is of potential therapeutic value for the suppression of complement-mediated tissue damage in vivo. An assay has been established using microtitre plates to explore the binding of sCR1 to the two isotypes of C4, C4A and C4B, and to C4 fragments. Specific binding of 125I-sCR1 to C4b and ammonia-treated C4 has been demonstrated. The binding of 125I-sCR1 to ammonia-treated C4 is dependent on pH and ionic strength, decreasing with an increase in pH and with an increase in ionic strength. At physiological ionic strength, up to twice as much 125I-sCR1 bound to ammonia-treated C4A as bound to ammonia-treated C4B. This preference of sCR1 for binding to the C4A isotype has implications for the clinical association of immune complex disease with C4A null alleles.
authors.affiliation: Department of Pharmacology, University of Oxford, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Gibb
authors.forename: A M
authors.initials: AM
authors.lastname: Freeman
authors.forename: R A
authors.initials: RA
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Edmonds
authors.forename: E
authors.initials: E
authors.lastname: Sim
mesh_terms: D000641:Ammonia / Q000494:pharmacology; D003181:Complement C4 / Q000378:metabolism*; D015934:Complement C4a / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011485:Protein Binding; D011951:Receptors, Complement / Q000378:metabolism*; D012965:Sodium Chloride; D012995:Solubility
chemical_list: D003181:Complement C4; D011951:Receptors, Complement; D012965:Sodium Chloride; D000641:Ammonia; D015934:Complement C4a; D015935:Complement C4b