Stevens J H, O'Hanley P, Shapiro J M, Mihm F G, Satoh P S, Collins J A, Raffin T A
J Clin Invest. 1986 Jun;77(6):1812-6. doi: 10.1172/JCI112506.
In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, control, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with anti-C5a antibodies did not die and did not develop decreased oxygenation (P less than 0.05) or increased extravascular lung water (P less than 0.05). They also had a marked recovery in their mean arterial blood pressure (P less than 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.
体外和体内研究表明，人补体成分C5a在成人呼吸窘迫综合征（ARDS）的中性粒细胞损伤中起关键作用。首先，我们使用白细胞凝集测定法证明，向内毒素激活的血浆中添加一种新开发的兔抗人C5a去精氨酸多克隆抗体可防止体外白细胞聚集。然后，我们将抗C5a去精氨酸抗体给予脓毒症灵长类动物（食蟹猴）。研究了三组灵长类动物，即对照组、脓毒症组和抗C5a抗体治疗的脓毒症组（每组n = 4）。输注大肠杆菌（1×10¹⁰ / kg）30分钟导致严重脓毒症和ARDS。在大肠杆菌输注完成后4小时处死灵长类动物。未用抗C5a抗体治疗的脓毒症动物死亡率为75%（3/4），氧合降低，严重肺水肿，且严重低血压。用抗C5a抗体治疗的脓毒症灵长类动物未死亡，也未出现氧合降低（P < 0.05）或血管外肺水增加（P < 0.05）。它们的平均动脉血压也有显著恢复（P < 0.05）。这项研究表明，用兔抗人C5a去精氨酸抗体治疗可减轻非人灵长类动物的ARDS和脓毒症的一些全身表现。
