NEUTROPHIL ADHESION RECEPTOR CD18 MEDIATES REMOTE BUT NOT LOCALIZED ACID ASPIRATION INJURY

NEUTROPHIL ADHESION RECEPTOR CD18 MEDIATES REMOTE BUT NOT LOCALIZED ACID ASPIRATION INJURY
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DOI:
10.1016/s0039-6060(05)80233-8
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发表时间:
1995-01-01
期刊:
影响因子:
3.8
通讯作者:
HECHTMAN, HB
HECHTMAN, HB
中科院分区:
医学2区
文献类型:
--
作者:
GOLDMAN, G;WELBOURN, R;HECHTMAN, HB

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背景资料。酸吸入导致肺多形核中性粒细胞(PMN)隔离和相关的通透性增加。尽管已知中性粒细胞黏附受体(CD18)在决定中性粒细胞在吸入区域的聚集方面没有作用,但我们推测这种PMN黏附受体及其内皮配体细胞间黏附分子-1(ICAM-1)介导了中性粒细胞的远程隔离。麻醉兔局部吸入0.1N盐酸0.1ml/kg(n=18)或生理盐水(n=18)。30分钟后出现白细胞减少,为2290+/-200个/mm(3)(p&lt;0.05)。吸痰后3h,吸出段肺泡灌洗液(X10(4))中的PMN积累量为87+/-6PMN/ml,对照组为6+/-1PMN/ml(p&lt;0.05)。出现了全身性肺白细胞减少的组织学证据。未吸出肺的湿/干重比由中央的3.9+/-0.1升至5.7+/-0.2(p&lt;0.05)。CD18单抗(R15.7,1 mg/kg)处理18只,对吸入节段中性粒细胞聚集无影响。然而,mAb可减轻远程炎症反应:早期白细胞减少(5790+/-400个/mm(3));肺白细胞计数(24+/-4个PMN/10高倍视野);支气管肺泡灌洗液中蛋白质渗漏(570+/-50mU/ml);以及水肿、湿/干重比(4.9+/-0.1)(均P<0.05)。ICAM-1单抗(RR1/1,1 mg/kg)治疗(n=9)不能减少中性粒细胞在吸入节段的聚集,但限制了远端炎症反应。酸吸入导致中性粒细胞黏附和远离通过中性粒细胞CD18和内皮细胞ICAM-1吸入的区域的水肿。
Background. Acid aspiration leads to lung polymorphonuclear neutrophil (PMN) sequestration and an associated increase in permeability. Although it is known that the neutrophil adhesion receptor (CD18) plays no role in determining PMN accumulations in the region aspirated, we postulated that this PMN adhesion receptor and its endothelial ligand, intercellular adhesion molecule-1 (ICAM-1), mediate remote neutrophil sequestration.Methods. Anesthetized rabbits underwent localized aspiration of either 0.1N HCl 0.1 ml/kg (n = 18) or saline solution (n = 18).Results. After 30 minutes leukopenia was noted, 2290 +/- 200 white blood cells/mm(3) (p < 0.05). At 3 hours diapedesis occurred in the aspirated segment with accumulations in bronchoalveolar lavage fluid (X10(4)) of 87 +/- 6 PMN/ml versus control of 6 +/- 1 PMN/ml (p < 0.05). Histologic evidence of generalized lung leukosequestration occurred. The wet to dry weight ratio of the nonaspirated lung rose to 5.7 +/- 0.2 versus central of 3.9 +/- 0.1 (p < 0.05). Treatment (n = 18) with the CD18 monoclonal antibody (mAb) (R15.7, 1 mg/kg) had no effect on neutrophil accumulations in the aspirated segment. However, the mAb attenuated the remote inflammatory response: early leukopenia (5790 +/- 400 white blood cells/mm(3)); lung leukosequestration (24 +/- 4 PMN/10 high-power fields); protein leak in bronchoalveolar lavage fluid (570 +/- 50 mu g/ml); and edema, wet to dry weight ratio (4.9 +/- 0.1) (all p < 0.05). Treatment with the ICAM-1 mAb (RR1/1, 1 mg/kg) (n = 9) did not reduce neutrophil accumulations in the aspirated segment but limited the remote inflammatory response.Conclusions. Acid aspiration leads to neutrophil adhesion and edema in regions remote from those aspirated via neutrophil CD18 and endothelial ICAM-1.