[Comparative effects of complement inhibitors in vitro and in vivo experiments: an immunoenzyme method in studying subcomponent C1q inhibition and complement inhibition in model animals].
Methods of analysis of inhibition of complement system in vitro and in vivo have been developed for study of effects of medical drugs on the complement. The first one, ELISA method, for determination of inhibition of the first stage of complement activation includes binding of C1q subcomponent to immunoglobulin. The second method is based on capacity of mink serum to kill mice at the intravenous administration due to the action of mink complement. The effects of heparin, known anticoagulant, and suramin, used for treatment of trypanosomiasis, have been studied using these systems. The inhibition constants of binding suramin and heparin binding evaluated by the first method C1q were 411 +/- 29 micrograms/ml (or 0.287 +/- 0.020 mumole/l) and 36.4 +/- 1.7 micrograms/ml (or 2.28 +/- 0.10 mmole/l), respectively. This indicates that heparin binding with C1q in 10 times is higher, than that for suramin (as weight ratio) or 100 times higher in molar ratio. Administration of 3 mg of suramin or 0.3 mg of heparin to mice protected them against lethal action of intravenously injected 0.08 ml of mink serum. Blood concentrations of these compounds approximately correspond to inhibition constants for C1q binding, obtained using in vitro method.
Kozlov
L V
LV
Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology, Ministry of Public Health of Russian Federation, ul. Admirala Makarova, 10, Moscow, 125212 Russia. L.V.Kozlov@mtu-net.ru
Belkin
Z P
ZP
Bichucher
A M
AM
Batalova
T N
TN
Diakov
V L
VL
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D015922:Complement C1q / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007106:Immune Sera / Q000737:chemistry / Q000506:poisoning; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D008297:Male; D051379:Mice; D008907:Mink; D011817:Rabbits; D013498:Suramin / Q000494:pharmacology
D000925:Anticoagulants; D007106:Immune Sera; D007074:Immunoglobulin G; D013498:Suramin; D015922:Complement C1q; D006493:Heparin