Complement-dependent immune complex-induced bronchial inflammation and hyperreactivity

Bronchoconstriction responses in the airway are caused by multiple insults and are the hallmark symptom in asthma. In an acute lung injury model in mi ce, IgG immune complex deposition elicited severe airway hyperreactivity th at peaked by 1 h, was maintained at 4 h, and was resolved by 24 h. The depl etion of complement with cobra venom factor (CVF) markedly reduced the hype rreactive airway responses, suggesting that complement played an important role in the response. Blockade of C5a with specific antisera also significa ntly reduced airway hyperreactivity in this acute lung model. Complement de pletion by CVF treatment significantly reduced tumor necrosis factor and hi stamine levels in bronchoalveolar lavage fluids, correlating with reduction s in airway hyperreactivity. To further examine the role of specific comple ment requirement, we initiated the immune complex response in C5-sufficient and C5-deficient congenic animals. The airway hyperreactivity response was partially reduced in the C5-deficient mice. Complement depletion with CVF attenuated airway hyperreactivity in the C5-sufficient mice but had a lesse r effect on the airway hyperreactive response and histamine release in bron choalveolar lavage fluids in C5-deficient mice. These data indicate that ac ute lung injury in mice after deposition of IgG immune complexes induced ai rway hyperreactivity that is C5 and C5a dependent.