Regulatory role of C5a anaphylatoxin on the Fcγ Rs effector system in immune complex-induced diseases

Excerpt

Enhanced effector cell activation to deposited autoantibodies and immune complexes (IC) is a significant factor causing inflammatory responses in immunologic diseases like autoimmune hemolytic anemia, rheumatoid arthritis, lupus nephritis and Goodpasture's syndrome. Recent studies in animal models show that the development of such diseases is caused by the impairment of balance between activating/inhibitory Fc receptors (FcγRs). The ratio of the opposing FcγRs is critical in determining whether an antibody-dependent response will result. In the present study we aimed to investigate the role of C5a anaphylatoxin on the FcγR effector system in IC lung injury. We analysed the reverse passive arthus reaction in the lungs of mice lacking different FcγRs, or C5aR. The expression of FcγR mRNA/protein on alveolar macrophages (AM) effector cells was studied by TaqMan real-time PCR and FACS analysis. The contribution of AM to the IC alveolitis was investigated using the AM-depletion/AM-transfer technique. The autocrine synthesis of C5a by AM and the role of G-protein-dependent signalling was studied using in vitro stimulation of MH-S AM cells with IgG₁ IC. …