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(American Journal of Pathology. 1999;154:1513-1524.)
© 1999 American Society for Investigative Pathology

Regular Articles

Synergistic Enhancement of Chemokine Generation and Lung Injury by C5a or the Membrane Attack Complex of Complement

Boris J. Czermak^*, Alex B. Lentsch, Nicolas M. Bless^*, Hagen Schmal^*, Hans Peter Friedl^* and Peter A. Ward

From the Department of Trauma Surgery,^*
University of Freiburg Medical School, Freiburg/Breisgau, Germany; the Department of Surgery,
University of Louisville School of Medicine, Louisville, Kentucky; and the Department of Pathology,
University of Michigan Medical School, Ann Arbor, Michigan

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

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