A codominant role of FcγRI/III and C5aR in the reverse Arthus reaction

Recent attempts to specify the relative contribution of FcR and complement in various experimental systems of immune complex disease have led to opposing conclusions. As concluded in IgG FcR gamma(-/-) mice, manifestation of disease is almost exclusively determined by Fc gamma R on effector cells, arguing for a minor role of complement. In contrast, data obtained with C5aR(-/-) mice suggested that, dependent on the tissue site, complement is more important than Fc gamma R. In this paper, we demonstrate that, in response to IgG immune complex formation, Fc gamma RI/III- and C5aR-mediated pathways are both necessary and only together are they sufficient to trigger the full expression of inflammation in skin and lung. Moreover, both effector systems are not entirely independent, suggesting an interaction between Fc gamma R and C5aR, Therefore, Fc gamma R-mediated responses can be integrated through C5aR activation, which may explain why these two receptor pathways have previously been considered to dominate each other.