中性粒细胞黏附受体CD18介导远距离而非局部酸性物质吸入性损伤。

Neutrophil adhesion receptor CD18 mediates remote but not localized acid aspiration injury.

作者信息

Goldman G, Welbourn R, Kobzik L, Valeri C R, Shepro D, Hechtman H B

机构信息

Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.

出版信息

Surgery. 1995 Jan;117(1):83-9. doi: 10.1016/s0039-6060(05)80233-8.

DOI:10.1016/s0039-6060(05)80233-8

PMID:7809841

Abstract

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/mm3 (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 control 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/mm3); lung leukosequestration (24 +/- 4 PMN/10 high-power fields); protein leak in bronchoalveolar lavage fluid (570 +/- 50 micrograms/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.

摘要

背景

酸吸入可导致肺多形核中性粒细胞（PMN）滞留，并伴有通透性增加。虽然已知中性粒细胞黏附受体（CD18）在决定吸入区域的PMN积聚中不起作用，但我们推测该PMN黏附受体及其内皮配体细胞间黏附分子-1（ICAM-1）介导远处中性粒细胞的滞留。

方法

对麻醉的家兔进行局部吸入0.1N盐酸0.1 ml/kg（n = 18）或生理盐水（n = 18）。

结果

30分钟后出现白细胞减少，白细胞计数为2290±200/mm³（p < 0.05）。3小时后，吸入段发生白细胞渗出，支气管肺泡灌洗液中PMN积聚量为87±6×10⁴/ml，而对照组为6±1×10⁴/ml（p < 0.05）。出现了肺部广泛性白细胞滞留的组织学证据。未吸入侧肺的湿重与干重之比升至5.7±0.2，而对照组为3.9±0.1（p < 0.05）。用CD18单克隆抗体（mAb）（R15.7，1 mg/kg）治疗（n = 18）对吸入段中性粒细胞的积聚无影响。然而，该mAb减轻了远处的炎症反应：早期白细胞减少（白细胞计数为5790±400/mm³）；肺部白细胞滞留（24±4个PMN/10个高倍视野）；支气管肺泡灌洗液中的蛋白质渗漏（570±50 μg/ml）；以及水肿，湿重与干重之比（4.9±0.1）（所有p < 0.05）。用ICAM-1 mAb（RR1/1，1 mg/kg）治疗（n = 9）并未减少吸入段中性粒细胞的积聚，但限制了远处的炎症反应。