Mechanism for the Isotype Dependence of Antibody-Mediated Toxicity in Cryptococcus neoformans-Infected Mice

摘要: Ab-based therapies have undergone a renaissance in recent years, but infusion-related reactions are significant clinical problem. Administration of certain mAbs to Swiss Webster mice infected with Cryptococcus neoformans can result acute lethal toxicity (ALT) characterized by cardiovascular collapse. The ability mAb produce ALT is isotype dependent and occurs IgG1 not IgG3. To investigate this phenomenon, we measured spleen liver cytokine responses platelet-activating factor (PAF) content given C. glucuronoxylomannan (GXM) followed specific Ab or IgG3 isotype. We found no evidence suggest that the differences were due chemokine response. In contrast, tissue PAF was significantly greater IgG1. Furthermore, our results show response IgG1- IgG3-GXM complexes regarding: 1) macrophage-inflammatory protein-1α monocyte chemoattractant protein-1 regulation, 2) splenic hepatic content, 3) mice. IgG1-associated appears be production IgG1-GXM complex formation. consistent view interact different Fc receptors. Our findings strongly mechanism for Ab-mediated from release syndrome described after administration other therapeutic mAbs.