CD16 and CR3 receptors distinguish between the two mechanisms of tumour cytotoxicity in neutrophils.
Previous studies have suggested that phorbol ester-activated neutrophils kill both antibody non-coated and antibody-coated K562 target cells. In this report the contribution of the receptors Fc gamma III (CD16) and CR3 (CD11b/CD18) in the lytic process was investigated. In neutrophils CD16 and CR3 are up-regulated by the phorbol ester up to 4 and 10 times, respectively. As expected, lysis of non-immunized K562 targets is not affected by the treatment of neutrophils with anti CD16, AB8.28, whereas lysis of immunized targets is decreased by 50%. In addition, the interaction of CD16 and AB8.28 induces calcium mobilization and increases granule secretion. Surprisingly, the simultaneous binding of AB8.28 and anti-CR3 OKM1 to neutrophils completely abolishes the lysis of antibody-coated targets. Unlike CD16, CR3 does not possess a functional role and binding of OKM1 to CR3 does not affect cytotoxicity of immunized K562 targets, but it blocks lysis of non-coated target almost completely, indicating a function as adhesion protein for CR3. These studies demonstrate a distinct role of CD16 and CR3 in mediating antibody-dependent and antibody-independent cellular cytotoxicity, respectively.
Gavioli
R
R
Istituto di Chimica Biologica, Università degli Studi di Ferrara, Italy.
Spisani
S
S
Giuliani
A L
AL
Cosulich
E
E
Risso
A
A
Traniello
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007938:Leukemia / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D013481:Superoxides / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D017452:Receptors, IgG; D013481:Superoxides; D002118:Calcium