[Inhibition of binding of activated compliment component C4b with its target].
The inhibition of covalent binding of the nascent C4b fragment of the human complement component to its natural target, immunoglobulin G, was studied. To this end, an immunoenzyme system was developed. In this ELISA method, the complement was activated on the sorbed IgG molecules and the resulting nascent C4b fragment acylated IgG or interacted with a competitive inhibitor added to the system. The inhibition constants for binding of the nascent C4b to its target were determined for immunoglobulins G1, G2, G3, G4, M, and A1, as well as for ferritin, yeast mannan, capsid polysaccharides of the Neisseria meningitidis A, B, and C serotypes, diphtheria anatoxin, epinephrine, and salicylic acid. On the basis of the experimental data, the immunoglobulin role at the activation stage of the complement regulation cascade, the relationship between the antigen immunogenicity and its ability to interact with C4b, and the direct effect of a number of therapeutic agents on the complement system were discussed. Lectins of various specificities were shown to inhibit the enzymic activation of C4 by the first complement component and the subsequent C4b sorption to its target, which allowed us to suggest that some oligosaccharide fragments of the C1s and C4 molecules are spatially close to the C1s active site and to the thioester bond of C4.
Kozlov
L V
LV
Gabrichevskii Research Institute of Epidemiology and Microbiology, Moscow, ul. Admirala Makarova 10, Moscow, 125212 Russia. l.v.kozlov@mtu-net.ru
Lakhtin
V M
VM
Skorokhodova
T G
TG
Batalova
T N
TN
Shoĭbonov
B B
BB
D'iakov
V L
VL
Guzova
V A
VA
Matveevskaia
N S
NS
D003167:Complement Activation; D015935:Complement C4b / Q000737:chemistry*; D004837:Epinephrine / Q000737:chemistry; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry*; D007075:Immunoglobulin M / Q000737:chemistry; D037102:Lectins / Q000737:chemistry; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D011485:Protein Binding; D020156:Salicylic Acid / Q000737:chemistry
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D037102:Lectins; D011135:Polysaccharides, Bacterial; D015935:Complement C4b; D020156:Salicylic Acid; D004837:Epinephrine