Park Jung-Won, Taube Christian, Joetham Anthony, Takeda Katsuyuki, Kodama Taku, Dakhama Azzeddine, McConville Glen, Allen Corrie B, Sfyroera Georgia, Shultz Lenny D, Lambris John D, Giclas Patricia C, Holers V Michael, Gelfand Erwin W
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Am J Respir Crit Care Med. 2004 Mar 15;169(6):726-32. doi: 10.1164/rccm.200307-1042OC. Epub 2003 Dec 30.
Ozone (O3) can induce airway hyperresponsiveness (AHR) and neutrophilic inflammation. We evaluated the role of complement in development of AHR and inflammation after acute O3 exposure in mice. Mice were exposed to O3 at 2 ppm for 3 hours, and airway responsiveness to methacholine was measured 8 hours after O3 exposure. Complement was depleted or inhibited by intraperitoneal injection of cobra venom factor (CVF) or complement receptor-related gene y (Crry)-Ig, a potent C3 convertase inhibitor; neutrophils were depleted using an antineutrophil monoclonal antibody. CVF attenuated the development of AHR by O3. Administration of Crry-Ig also prevented the development of AHR. Bronchoalveolar lavage (BAL) fluid neutrophilia after O3 exposure was significantly decreased by administration of either CVF or Crry-Ig. Increased BAL fluid total protein after O3 exposure was lowered by depletion or inhibition of complement. In contrast to the effects of complement inhibition or depletion, depletion of BAL neutrophil counts by more than 90% with the monoclonal antibody did not affect the development of AHR after O3 exposure. These data indicated that activation of the complement system follows acute O3 exposure and is important to the development of AHR and airway neutrophilia. However, this neutrophil response does not appear necessary for the development of AHR.
臭氧（O₃）可诱发气道高反应性（AHR）和中性粒细胞炎症。我们评估了补体在小鼠急性暴露于O₃后AHR和炎症发展中的作用。将小鼠暴露于2 ppm的O₃中3小时，并在O₃暴露8小时后测量气道对乙酰甲胆碱的反应性。通过腹腔注射眼镜蛇毒因子（CVF）或补体受体相关基因y（Crry）-Ig（一种有效的C3转化酶抑制剂）来消耗或抑制补体；使用抗中性粒细胞单克隆抗体清除中性粒细胞。CVF减弱了O₃诱导的AHR的发展。给予Crry-Ig也可预防AHR的发展。给予CVF或Crry-Ig可显著降低O₃暴露后支气管肺泡灌洗（BAL）液中的中性粒细胞增多。O₃暴露后BAL液中总蛋白的增加通过补体的消耗或抑制而降低。与补体抑制或消耗的作用相反，用单克隆抗体使BAL中性粒细胞计数减少90%以上并不影响O₃暴露后AHR的发展。这些数据表明，补体系统的激活发生在急性O₃暴露之后，并且对AHR和气道中性粒细胞增多的发展很重要。然而，这种中性粒细胞反应似乎不是AHR发展所必需的。
