Heuertz R M, Piquette C A, Webster R O
Cell and Molecular Biology Program, St. Louis University School of Medicine, Missouri.
Am J Pathol. 1993 Jan;142(1):319-28.
In previous studies, we have shown that C-reactive protein (CRP) inhibits chemotaxis of neutrophils to complement fragments in vitro. To evaluate the effect of CRP on C5a-induced inflammation in vivo, a rabbit model of alveolitis was used. Rabbits pretreated with subcutaneous injections of croton oil had serum CRP increase from undetectable levels to 270 +/- 70 micrograms/ml 48 hours later. Rabbits were intubated and C5a des arg (10 micrograms/ml) instilled directly into the lungs via an endotracheal tube. Four to six hours later, the animals were killed and bronchoalveolar lavage performed. Rabbits pretreated with croton oil had significantly (P < 0.01) reduced C5a des arg-stimulated neutrophil infiltration (30 +/- 5%) into alveolar air spaces compared to untreated rabbits (64 +/- 9%). Increased numbers of total leukocytes in the alveolar washes coincided with increased neutrophil numbers whereas alveolar macrophages remained unchanged in all groups. Rabbits pretreated with croton oil also had a significant decrease (P < 0.05) in total protein (320 +/- 50 micrograms/ml) in lavage fluid after C5a instillation compared with untreated animals (850 +/- 140 micrograms/ml). In vitro, rabbit CRP (50 micrograms/ml) added to normal rabbit serum significantly (P < 0.05) inhibited chemotaxis of human neutrophils by 41%. Finally, direct intravenous pretreatment of rabbits with purified CRP also significantly reduced C5a-induced alveolitis. The CRP-C5a group had 33 +/- 10% neutrophil infiltration, a significant (P < 0.01) reduction from the C5a group (71 +/- 6%). The total protein content of the CRP-C5a rabbits was 986 +/- 165 micrograms/ml in the lavage fluid, which was significantly (P < 0.05) lower than the C5a group (1645 +/- 363 micrograms/ml). Therefore, CRP inhibits the development of neutrophil alveolitis and protein leakage in vivo and inhibits neutrophil chemotaxis in vitro. These data indicate that CRP offers a protective effect in neutrophil-mediated lung injury by reducing neutrophil influx and protein leak.
在先前的研究中，我们已经表明，C反应蛋白（CRP）在体外可抑制中性粒细胞对补体片段的趋化作用。为了评估CRP对体内C5a诱导的炎症的影响，我们使用了兔肺泡炎模型。皮下注射巴豆油预处理的兔子，其血清CRP在48小时后从检测不到的水平升高至270±70微克/毫升。将兔子插管，通过气管内导管将C5a去精氨酸（10微克/毫升）直接注入肺中。4至6小时后，处死动物并进行支气管肺泡灌洗。与未处理的兔子（64±9%）相比，经巴豆油预处理的兔子C5a去精氨酸刺激的中性粒细胞浸润到肺泡腔中的比例显著降低（P<0.01）（30±5%）。肺泡灌洗液中总白细胞数量的增加与中性粒细胞数量的增加一致，而所有组中的肺泡巨噬细胞数量保持不变。与未处理的动物（850±140微克/毫升）相比，经巴豆油预处理的兔子在注入C5a后，灌洗液中的总蛋白（320±50微克/毫升）也显著降低（P<0.05）。在体外，向正常兔血清中添加兔CRP（50微克/毫升）可显著（P<0.05）抑制人中性粒细胞趋化作用达41%。最后，用纯化的CRP对兔子进行直接静脉预处理也显著减轻了C5a诱导的肺泡炎。CRP-C5a组的中性粒细胞浸润率为33±10%，与C5a组（71±6%）相比显著降低（P<0.01）。CRP-C5a组兔子灌洗液中的总蛋白含量为986±165微克/毫升，显著低于C5a组（1645±363微克/毫升）（P<0.05）。因此，CRP在体内可抑制中性粒细胞肺泡炎的发展和蛋白渗漏，并在体外抑制中性粒细胞趋化作用。这些数据表明，CRP通过减少中性粒细胞流入和蛋白渗漏，对中性粒细胞介导的肺损伤具有保护作用。
