Relative inefficiency of terminal complement activation.
The efficiency of generation of fluid-phase SC5b-9 and membrane C5b-9(m) complexes relative to cleavage of C3 and C5 was studied. Fluid-phase C activation was induced through addition of purified bacterial Ag to human serum. Sephadex beads were used as particulate activators of the alternative pathway. Rabbit or antibody-coated sheep or human E were used to study formation of cytolytic C5b-9(m) complexes. The molar ratios of C3a:C5a generated in the model systems were found to be in the range of 60 to 200:1 in the case of soluble immune complex activators, and 70 to 150:1 with particulate activators and cells. The efficiency of C5 cleavage relative to C3 cleavage increased on surfaces with the density of antibody and/or C3b-binding sites. With soluble immune complexes, the efficiency of subsequent SC5b-9 generation displayed wide variations dependent on Ag and donor with molar ratios of C5a:SC5b-9 ranging from 30:1 for teichoic acid and sometimes approaching 1:1 for streptolysin-O. In contrast, activation on particles or cells always led to C5a:C5b-9 (calculated as the sum of generated moles SC5b-9 and C5b-9(m] ratios approaching 1:1. Hence, there is an overall inefficiency of terminal sequence activation in the C cascade due first to a dissociation at the level of C5 convertase formation/C5-cleavage and second, to a frequent inefficiency of C5b-utilization in the fluid-phase. The results provide an explanation for the very low levels of SC5b-9 found in plasma of healthy individuals and in patients with C-consuming immune complex disease.
Bhakdi
S
S
Institute of Medical Microbiology, University of Giessen, West Germany.
Fassbender
W
W
Hugo
F
F
Carreno
M P
MP
Berstecher
C
C
Malasit
P
P
Kazatchkine
M D
MD
D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology; D003167:Complement Activation; D003176:Complement C3 / Q000096:biosynthesis / Q000378:metabolism; D015926:Complement C3a; D003182:Complement C5 / Q000096:biosynthesis / Q000378:metabolism*; D015936:Complement C5a; D015938:Complement Membrane Attack Complex; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000096:biosynthesis / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis; D006801:Humans; D008863:Microspheres; D011817:Rabbits; D012756:Sheep
D000936:Antigen-Antibody Complex; D003176:Complement C3; D003182:Complement C5; D015938:Complement Membrane Attack Complex; D015926:Complement C3a; D015936:Complement C5a; D003165:Complement System Proteins