Aspiration-induced lung injury: Role of complement

Objectives: To examine the role of complement in the development of acid aspiration-induced lung injury in the rat. It was postulated that inhibition or depletion of complement attenuates aspiration-induced lung injury. Design: Controlled animal trial. Setting: Animal Laboratory, Jefferson Medical College, Philadelphia, PA. Subjects: Anesthetized rats. Interventions: Aspiration was induced by the intratracheal administration of 0.2 mL of 0.1 N hydrochloric acid (n = 7) and lung injury was evaluated by determining water content, myeloperoxidase activity, protein concentration, and leukocyte count in bronchoalveolar lavage fluid. Muscle PO₂ was directly measured using a thin-film chamber oxygen sensor and serum tumor necrosis factor-α was assayed by enzyme-linked immunosorbent assay. The effect of complement inhibition by recombinant human soluble complement receptor type 1 (n = 8) or complement depletion by cobra venom factor (n = 7) on lung injury was evaluated. Measurements and Main Results: Acid aspiration induced pulmonary leukosequestration, edema, and a microvascular permeability defect, along with tissue hypoxia. Pretreatment with soluble complement receptor type 1 (complement inhibition) or cobra venom factor (complement depletion) significantly reduced lung edema (-61 ± 7% ;p < .05), eliminated protein accumulation in bronchoalveolar lavage fluid (p < .01), and improved (p < .05) tissue oxygenation. In contrast, there was no effect of soluble complement receptor type 1 or of cobra venom factor on leukosequestration. Conclusions: Acid aspiration induces lung injury through a complement- dependent mechanism that leads to microvascular permeability defects. Therefore, the possibility that complement inhibitors may have a salutary effect in humans with aspiration-induced lung injury should be investigated.