Requirement for C5a in lung vascular injury following thermal trauma to rat skin

Previous studies in rats have shown that deep second degree dermal burns, involving 28-30% of total body surface area, result in systemic complement activation, appearance in plasma of chemotactic activity, sequestration of blood neutrophils in lung capillaries, and development of neutrophil-dependent dermal vascular and lung vascular injury. Although blockade of complement activation or depletion of complement before skin burns has resulted in significant attenuation of tissue injury both locally and distally (in lung), a role for C5a in these events is unclear. In the following studies, we demonstrate the presence of C5a and neutrophil chemotactic activity in serum and in lung homogenates after thermal injury. C5a has also been found in bronchoalveolar lavage fluids of thermally injured animals. Treatment of animals with a polyclonal neutralizing rabbit antibody to rat C5a was lung protective. The protective effects of the antibody (anti-C5a) were associated with diminished vascular permeability changes, as well as reduced tissue build-up of myeloperoxidase. Anti-C5a also prevented up-regulation of lung vascular ICAM-1 (intercellular adhesion molecule-1) in skin-burned rats. These observations indicate that C5a is essential for development of neutrophil accumulation and vascular permeability increases in distant (lung) organs after thermal trauma to skin. The protective effects of anti-C5a in lung, appear to be related to prevention of up-regulation of vascular ICAM-1. Accordingly, C5a may represent a target for clinical approaches in the treatment of organ injury following thermal trauma.