J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/08/749/08 $2.00
Volume 186, Number 5, August 29, 1997 749-756

Impaired Inflammatory Responses in the Reverse Arthus Reaction Through Genetic Deletion of the C5a Receptor

By Uta E. Höpken,^* Bao Lu,^* Norma P. Gerard,^* and Craig Gerard^*

From the ^* Ina Sue Perlmutter Cystic Fibrosis Laboratory and Department of Pediatrics, Children's Hospital, Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02115

We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex-mediated inflammation. In this study, we compare the effect of C5aR deficiency in immune complex-induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model. C5aR- deficient mice exhibit decreased migration of neutrophils and decreased levels of TNF- and interleukin 6 in the peritoneal reverse passive Arthus reaction compared to their wild-type littermates. In the reverse passive Arthus reaction in the skin the C5aR was also required for the full expression of neutrophil influx and edema formation; C5aR-deficient mice showed reduced neutrophil migration and microvascular permeability changes. In contrast to our studies in immune complex-induced lung inflammation, C5aR deficiency does not completely prevent injury in the peritoneal cavity and skin. These data indicate a dominant role for the C5aR and its ligand in the reverse passive Arthus reaction in the lung and a synergistic role together with other inflammatory mediators in immune complex-mediated peritonitis and skin injury.

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