Effect of CD14 blockade in rabbits with Escherichia coli pneumonia and sepsis
Effect of CD14 blockade in rabbits with Escherichia coli pneumonia and sepsis
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DOI：
10.4049/jimmunol.164.10.5439
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发表时间：
2000-05-15
影响因子：
4.4
通讯作者：
Martin, TR
中科院分区：
文献类型：
--
作者：
Frevert, CW;Matute-Bello, G;Martin, TR
CD 14是在骨髓细胞上发现的模式识别受体，是先天免疫系统的关键组分，其介导对革兰氏阴性和革兰氏阳性细菌产物的局部和全身宿主应答。先前在正常动物中的研究已经测试了CD 14阻断对静脉内LPS的全身反应的影响。本研究的目的是确定CD 14阻断剂是否能预防大肠杆菌肺炎相关的有害全身反应，并确定该策略是否影响肺组织感染的反应。用2.5 mg/kg的抗CDI 4 mAb或同种型对照mAb预处理兔。E.大肠杆菌（1 × 10（9）CFU）接种到肺中，观察动物4或24小时。阻断CD 14可改善平均动脉血压（p = 0.001），减少静脉输液需求（p = 0.01）。虽然这种治疗保护了血管室，但抗CD 14 mAb治疗的兔增加了从灌注肺中回收的支气管肺泡灌洗液中的细菌负荷（p = 0.005），并扩大了肺泡-动脉氧差。阻断CD 14可以预防败血症中发生的有害全身反应;然而，其他措施对于控制原发感染部位的细菌增殖是必要的。
CD14, a pattern recognition receptor found on myeloid cells, is a critical component of the innate immune system that mediates local and systemic host responses to Gram-negative and Gram-positive bacterial products. Previous studies in normal animals have tested the effect of CD14 blockade on the systemic response to i.v. LPS. The goals of the study were to determine whether CD14 blockade protected against the deleterious systemic response associated with Escherichia coli pneumonia and to determine whether this strategy affected the pulmonary response to tissue infection. Rabbits were pretreated,vith either anti-CDI4 mAb or isotype control mAb at 2.5 mg/kg. E. coli (1 x 10(9) CFU) was inoculated into the lungs, and the animals were observed for either 4 or 24 h, The blockade of CD14 improved the mean arterial blood pressure (p = 0.001) and decreased the i.v. fluid requirements (p = 0.01). Although this therapy protected the vascular compartment, rabbits treated,vith anti-CD14 mAb had increased bacterial burdens in the bronchoalveolar lavage fluid recovered from the instilled lung (p = 0.005) and widened alveolar-arterial oxygen difference. Blockade of CD14 prevents the deleterious systemic responses that occur in sepsis; however, other measures are necessary to control bacterial proliferation at the primary site of infection.