Two distinct mechanisms of cytotoxicity by porcine alveolar macrophages in antibody-dependent and immobilized immune complex-dependent cellular cytotoxicity.
The mechanisms of cytotoxicity by porcine pulmonary alveolar macrophages (PAM) involved in antibody-dependent cellular cytotoxicity (ADCC) and immobilized immune complex-dependent cellular cytotoxicity (IIC-DCC) were investigated. The results indicate that IIC-DCC was inhibited by both catalase and thioglycollate broth whereas these peroxide scavengers had no effect on ADCC in an 18-hr chromium-release assay. Furthermore, it was found that when the PAM and red blood cell targets were cross-linked with PHA, catalase still completely eliminated IIC-DCC and had no effect on ADCC, which suggests that catalase is able to penetrate the lytic site when the effector and targets are cross-linked as in ADCC. The presence of cytochalasin B, which inhibits internalization of immune complexes by PAM and presumably prevents intracellular killing, also had no effect on the differential susceptibility of IIC-DCC and ADCC to catalase. Finally, it is shown that the nonspecific cytotoxicity generated by exposing PAM to immune complexes in suspension in conjunction with cytochalasin B, so that the immune complex-bound Fc receptor (FcR) cannot be internalized, also was susceptible to catalase. These data show that the lytic mechanism involved in the nonspecific cytotoxicity generated by exposing PAM to immobilized immune complexes or immune complexes in suspension in conjunction with cytochalasin B, both of which prevent the internalization of immune complex-bound FcR, is mediated solely by peroxide whereas the lytic mechanism involved in ADCC operates, at least partially, through a peroxide-independent mechanism.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology; D002645:Chickens; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology; D013552:Swine; D013556:Swine, Miniature; D013864:Thioglycolates / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D003432:Cross-Linking Reagents; D010835:Phytohemagglutinins; D013864:Thioglycolates; D003571:Cytochalasin B; D006861:Hydrogen Peroxide; D002374:Catalase