REQUIREMENT FOR C5A IN LUNG VASCULAR INJURY FOLLOWING THERMAL TRAUMA TO RAT SKIN

Previous studies in rats have shown that deep second degree dermal bur ns, involving 28-30% of total body surface area, result in systemic co mplement activation, appearance in plasma of chemotactic activity, seq uestration of blood neutrophils in lung capillaries, and development o f neutrophil-dependent dermal vascular and lung vascular injury. Altho ugh blockade of complement activation or depletion of complement befor e 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 lavag e fluids of thermally injured animals. Treatment of animals with a pol yclonal neutralizing rabbit antibody to rat C5a was lung protective. T he protective effects of the antibody (anti-C5a) were associated with diminished Vascular permeability changes, as well as reduced tissue bu ild-up of myeloperoxidase. Anti-C5a also prevented up-regulation of lu ng vascular ICAM-1 (intercellular adhesion molecule-1) in skin-burned rats. These observations indicate that C5a is essential for developmen t of neutrophil accumulation and vascular permeability increases in di stant (rung) organs after thermal trauma to skin. The protective effec ts of anti-C5a in lung, appear to be related to prevention of up-regul ation of vascular ICAM-1. Accordingly, C5a may represent a target for clinical approaches in the treatment of organ injury following thermal trauma.