Synergistic enhancement of chemokine generation and lung injury by C5a or the membrane attack complex of complement

Complement plays an important role in many acute inflammatory responses. In the current studies it was demonstrated that, in the presence of either C5 a or sublytic forms of the complement-derived membrane attack complex (MAC) , rat alveolar macrophages costimulated with IgG immune complexes demonstra ted synergistic production of C-X-C (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) and C-C (macrophage inflammato ry protein-1 alpha and monocyte chemoattractant-l) chemokines. In the absen ce of the costimulus, C5a or MAC did not induce chemokine generation. In in vivo studies, C5a and MAC alone caused limited or no intrapulmonary genera tion of chemokines, but in the presence of a costimulus (IgG immune complex es) C5a and MAC caused synergistic intrapulmonary generation of C-X-C and C -C chemokines but not of tumor necrosis factor alpha. Under these condition s increased neutrophil accumulation occurred, as did lung injury. These obs ervations suggest that C5a and MAC function synergistically with a costimul us to enhance chemokine generation and the intensity of the lung inflammato ry response.