Systemic complement system depletion does not inhibit cellular accumulation in antihistamine pretreated allergic guinea pig lung

The present study was designed to determine if depletion of the complement system in the circulation with cobra venom factor (CVF) prevented the cellular infiltration in a guinea pig model of asthma. Guinea pigs were sensitized with ovalbumin (OA) alone or OA with complete Freund’s adjuvant. Animals were pretreated with CVF and challenged with OA aerosol for 15 min in the presence of the antihistamine pyrilamine. Either 6 or 20 h later, bronchoalveolar lavage (BAL) was collected and the numbers of white blood cells and red blood cells and amount of protein were determined. In addition, eosinophil peroxidase and myeloperoxidase activity of the lavage and lung homogenate was measured as an indicator of eosinophil and neutrophil infiltration. Aerosol OA challenge caused cellular infiltration in the lung and BAL. CVF treatment did not inhibit the OA-induced cellular infiltration but resulted in an enhanced accumulation of eosinophils 6 h after OA and increased protein in the lavage at 20 h after OA compared to animals not treated with CVF and challenged with OA. Total hemolytic complement activity in the serum was reduced by more than 98% and local complement activity (C3 in the BAL) by more than 95% by CVF treatment. However, after OA challenge in CVF-treated animals, the C3 content of the BAL was not different from control. Thus, leakage of plasma proteins or local synthesis of C3 induced by OA was sufficient to maintain C3 at normal levels in the BAL despite drastic reductions in C3 in the circulation (> 98%) by CVF treatment. Our studies indicate that the systemic complement system is not essential for the cellular infiltration in this guinea pig model of asthma. Complement in local compartments may have an important role in inflammatory events in the lung. In addition, complement system depletion and/or activation may be an important determinant of the severity of a subsequent allergic reaction.