Cross-linking of immune complexes by human mononuclear phagocytes

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Immune complexes (IC) can activate immune cells.
• The molecular mechanisms of IC-mediated cellular responses are not fully understood.

Purpose of the Study:

• To investigate the mechanisms of protein cross-linking in IC bound to human monocytes.
• To elucidate the role of oxidative processes in IC cross-linking.

Main Methods:

• Incubation of IC-bound antibodies with human monocytes.
• Assessment of antibody cross-linking using chaotropic solutions and acid pH.
• Quantification of immunoglobulin using enzyme-linked immunoassay.
• Evaluation of the role of hydrogen peroxide, oxygen metabolites, and enzymes.

Main Results:

• Monocytes induced cross-linking of antibodies in IC, which was inhibited by sodium azide.
• Catechol addition significantly increased IC cross-linking, dependent on viable phagocytic cells.
• The process was mediated by hydrogen peroxide and azide-inhibitable enzymes, likely monocyte-peroxidase.
• Catalase abolished cross-linking, suggesting hydrogen peroxide's critical role.

Conclusions:

• Catechol-dependent IC cross-linking involves oxidation to orthoquinone, leading to nonenzymic protein modification.
• Cell-mediated oxidative cross-linking of IC may contribute to inflammatory processes and drug reactions.