C1q enhancement of antibody-dependent granulocyte-mediated killing of nonphagocytosable targets in vitro.
A possible role for C1q in antibody-dependent granulocyte-mediated killing of nonphagocytosable targets was investigated utilizing IgG-dependent granulocyte cytotoxicity directed against microfilariae of Dirofilaria immitis. Granulocyte-mediated killing of microfilariae is enhanced by addition of fresh serum. Lack of C4 did not significantly reduce the observed increase in cytotoxicity. The addition of highly purified monomeric human Clq (0.2 microgram/ml) in the presence of immune IgG resulted in a two- to fivefold enhancement of killing (P less than 0.025). C1q enhancement of killing occurred in the absence of fluid-phase IgG, but killing was significantly less than when both fluid-phase IgG and C1q were present. The effect of C1q was inhibited by the addition of solubilized type I collagen (44-92% inhibition of killing, P less than 0.05). Significant 125I-Clq binding to microfilariae occurred only in the presence of immune IgG. In addition, C1q in concentrations ranging from 0.5 to 2.0 micrograms/ml resulted in a dose-dependent increase in binding of 125I-immune IgG to microfilariae. Finally, when purified C1q was added to preopsonized, washed microfilariae, granulocyte production of superoxide was increased from 0.25 +/- 0.07 to 0.68 +/- 0.07 nm/10(6) cells.10 min (P less than 0.01). These results describe a novel functional role for C1q in enhancement of antibody-dependent cellular cytotoxicity towards nonphagocytosable targets.
Hamada
A
A
Department of Medicine, Case Western Reserve University, Cleveland, Ohio.
Young
J
J
Chmielewski
R A
RA
Greene
B M
BM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D003166:Complement Activating Enzymes / Q000378:metabolism / Q000502:physiology*; D003172:Complement C1 / Q000378:metabolism / Q000502:physiology*; D015922:Complement C1q; D004183:Dirofilaria immitis / Q000276:immunology; D004285:Dogs; D006098:Granulocytes / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008562:Membrane Glycoproteins; D008842:Microfilariae / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D011951:Receptors, Complement / Q000032:analysis; D011961:Receptors, Fc / Q000276:immunology; D013481:Superoxides / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D003172:Complement C1; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D011961:Receptors, Fc; C032402:complement 1q receptor; D013481:Superoxides; D015922:Complement C1q; D003094:Collagen; D003166:Complement Activating Enzymes