Diethylcarbamazine-enhanced activation of complement by intact microfilariae of Dirofilaria immitis and their in vitro products.
Microfilariae of Dirofilaria immitis and their products inhibited hemolytic complement in sera from various animal species. Inhibition of hemolytic complement activity, fluorescent antibody detection of specific complement proteins binding to microfilarial surfaces, and immunoelectrophoretic evaluation of complement protein C3 conversion demonstrated that (1) intact microfilariae depleted hemolytic complement activity maximally in the presence of diethylcarbamazine whereas the complement-fixing activity of microfilarial products was little affected by diethylcarbamazine; (2) complement proteins C3, properdin, and C5 bound to the cuticular surface of microfilariae; and (3) C3 was converted to a faster-migrating species during incubation with microfilariae or their products. The complement-depleting activity of in vitro products from viable microfilariae was soluble in 10% trichloroacetic acid, resistant to beta-elimination with 0.5 M NaOH, susceptible to treatment with 0.2 M periodate, and composed of 56% neutral sugar, 18% protein, 12% hexosamine, and 10% sulfate. The polysulfated, acidic mucopolysaccharide nature of the surfaces of microfilariae and the results presented here indicate that polyanionic components on worm surfaces or shed by microfilariae react with host complement proteins. This interaction may be enhanced by diethylcarbamazine and contribute to the pathology associated with microfilaremias.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D003167:Complement Activation / Q000187:drug effects; D003176:Complement C3 / Q000032:analysis; D004049:Diethylcarbamazine / Q000494:pharmacology*; D004182:Dirofilaria / Q000254:growth & development / Q000276:immunology*; D004285:Dogs; D005370:Filarioidea / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis
D000954:Antigens, Surface; D003176:Complement C3; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D004049:Diethylcarbamazine