REQUIREMENT AND ROLE OF C5A IN ACUTE LUNG INFLAMMATORY INJURY IN RATS

The complement activation product, C5a, may play a key role in the acu te inflammatory response. Polyclonal antibody to rat C5a was used to d efine the requirements for C5a in neutrophil-dependent inflammatory lu ng injury after systemic activation of complement by cobra venom facto r (CVF) or after intrapulmonary deposition of IgG immune complexes. In the CVF model, intravenous infusion (but not intratracheal instillati on) of anti-C5a produced a dose-dependent reduction in lung permeabili ty and in lung content of myeloperoxidase. In C6-deficient rats, CVF i nfusion caused the same level of lung injury (measured by leak of I-12 5-albumin) as found in C6-sufficient rats. In the IgG immune complex m odel of lung injury, anti-C5a administered intratracheally (but not in travenously) reduced in a dose-dependent manner both the increase in l ung vascular permeability as well as the buildup of lung myeloperoxida se. Treatment with anti-C5a greatly suppressed upregulation of lung va scular intercellular adhesion molecule-1 (ICAM-1). This was correlated with a substantial drop in levels of TNF alpha in bronchoalveolar flu ids. These data demonstrate the requirement for C5a in the two models of injury. In the IgG immune complex model, C5a is required for the fu ll production of TMF alpha and the corresponding upregulation of lung vascular ICAM-1.