Functional properties of heterogeneous human asialo-C4 and its isotypes C4A and C4B.
The fourth component of human complement (C4) is encoded at two separate but closely linked loci within the MHC on the short arm of chromosome 6. Thus, there are two types of C4 protein in most individual and pooled normal human sera (NHS): C4A and C4B. Incubation of individual sera, pooled NHS, or purified heterogeneous C4 (C4A/C4B) with bacterial sialidase at 37 degrees C increased C-mediated hemolysis of antibody-sensitized sheep erythrocytes 1.54- to 1.93-fold. Comparative studies of Tmax of human C2, using asialo-C4 or buffer-treated C4 on EAC1gp and extrapolation to time 0 indicated a z value 4-fold higher with asialo-C4. This indicated that more hemolytically active C42 complexes are available with sialidase-treated C4 compared to untreated C4. There was no appreciable difference in the % 125I-C4 bound to EAC1gp (sialidase- or buffer-treated). Sera from two different blood donors with C4A3 phenotype (C4BQ0), two different donors with C4B1 phenotype (C4AQ0), and serum from an individual heterozygous deficient at both C4A3 and C4B1 regions (A3, AQ0; B1, BQ0) were investigated. The C4 allotypes, purified from these sera, were treated with sialidase; the C4A3 was enhanced in hemolytic assays by sialidase-treatment (1.52- to 2.3-fold), whereas the C4B1 allotype was not enhanced. Fluorometric determinations revealed that approximately the same percentage of sialic acid was released from sialidase-treated C4A3 and C4B1. Therefore, the increase in hemolytic titer observed after treatment of NHS or purified heterogeneous C4 with sialidase is a property of C4A3 but not a property of C4B1.
Schultz
D R
DR
Department of Medicine, University of Miami School of Medicine, Florida.
Arnold
P I
PI
D001212:Asialoglycoproteins / Q000302:isolation & purification / Q000502:physiology*; D002021:Buffers; D003175:Complement C2 / Q000187:drug effects / Q000502:physiology; D003181:Complement C4 / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D015934:Complement C4a / Q000502:physiology; D015935:Complement C4b / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D009439:Neuraminidase / Q000493:pharmacokinetics / Q000494:pharmacology
D001212:Asialoglycoproteins; D002021:Buffers; D003175:Complement C2; D003181:Complement C4; D015934:Complement C4a; D015935:Complement C4b; D009439:Neuraminidase