Regal J F, Fraser D G
Department of Pharmacology, University of Minnesota Duluth 55812-2487, USA.
Int Arch Allergy Immunol. 1996 Feb;109(2):150-60. doi: 10.1159/000237214.
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.
本研究旨在确定用眼镜蛇毒因子（CVF）消耗循环系统中的补体系统是否能预防豚鼠哮喘模型中的细胞浸润。豚鼠单独用卵清蛋白（OA）或用完全弗氏佐剂的OA进行致敏。动物先用CVF预处理，然后在抗组胺药吡拉明存在的情况下用OA气雾剂激发15分钟。6小时或20小时后，收集支气管肺泡灌洗（BAL）液，测定白细胞、红细胞数量和蛋白含量。此外，测量灌洗液和肺匀浆中嗜酸性粒细胞过氧化物酶和髓过氧化物酶活性，作为嗜酸性粒细胞和中性粒细胞浸润的指标。OA气雾剂激发导致肺和BAL中的细胞浸润。CVF治疗并未抑制OA诱导的细胞浸润，但与未用CVF治疗且用OA激发的动物相比，在OA激发后6小时导致嗜酸性粒细胞积累增加，在OA激发后20小时灌洗液中的蛋白增加。CVF治疗使血清中的总溶血补体活性降低超过98%，局部补体活性（BAL中的C3）降低超过95%。然而，在CVF处理的动物中进行OA激发后，BAL中的C3含量与对照组无差异。因此，尽管CVF治疗使循环中的C3大幅降低（>98%），但OA诱导的血浆蛋白渗漏或C3的局部合成足以使BAL中的C3维持在正常水平。我们的研究表明，在这个豚鼠哮喘模型中，全身补体系统对于细胞浸润并非必不可少。局部区域的补体可能在肺部炎症事件中起重要作用。此外，补体系统的消耗和/或激活可能是随后过敏反应严重程度的重要决定因素
