Burns A R, Takei F, Doerschuk C M
Pulmonary Research Laboratory, University of British Columbia, St. Paul's Hospital, Vancouver, Canada.
J Immunol. 1994 Oct 1;153(7):3189-98.
In the systemic circulation, neutrophil emigration into sites of acute inflammation is mediated through the leukocyte adhesion complex, CD11/CD18. ICAM-1 is an inducible endothelial ligand for CD11a/CD18 and CD11b/CD18. Streptococcus pneumoniae elicits neutrophil emigration through a CD18-independent mechanism whereas Escherichia coli endotoxin elicits emigration through a CD18-dependent mechanism in rabbit lungs. To determine whether ICAM-1 is up-modulated in the lung during CD18-independent and CD18-dependent emigration, ultrastructural immunogold-labeling studies were performed on BALB/c mice given airway instillates of S. pneumoniae or E. coli endotoxin. Ultrathin cryosections of frozen lung tissue were immunogold labeled with the mAb YN1/1.7.4 against the murine homologue of human ICAM-1. Gold particles on the plasma membranes of alveolar endothelial and epithelial cells were quantitated by transmission electron microscopy. Capillary endothelial ICAM-1 expression did not change during neutrophil emigration toward S. pneumoniae, a CD18-independent pathway in rabbits. In contrast, ICAM-1 expression increased 4.2-fold in response to E. coli endotoxin (known to elicit CD18-dependent emigration in mice), suggesting that the mechanism of adhesion may be regulated by the expression of endothelial rather than neutrophil adhesion molecules. Constitutive expression of ICAM-1 on alveolar epithelial cells was 22-fold greater than on capillary endothelium. Epithelial expression was mainly restricted to type I pneumocytes, whereas type II pneumocytes, the precursors of type I cells, expressed little or no ICAM-1. However, during pneumonia, type II but not type I pneumocytes showed increased ICAM-1 expression, suggesting that ICAM-1 expression represents an early differentiation even in response to epithelial injury.
在体循环中，中性粒细胞迁移至急性炎症部位是通过白细胞黏附复合体CD11/CD18介导的。细胞间黏附分子-1（ICAM-1）是CD11a/CD18和CD11b/CD18的诱导性内皮配体。肺炎链球菌通过一种不依赖CD18的机制引发中性粒细胞迁移，而大肠杆菌内毒素在兔肺中通过一种依赖CD18的机制引发迁移。为了确定在不依赖CD18和依赖CD18的迁移过程中肺内ICAM-1是否上调，对经气道滴注肺炎链球菌或大肠杆菌内毒素的BALB/c小鼠进行了超微结构免疫金标记研究。用针对人ICAM-1鼠同源物的单克隆抗体YN1/1.7.4对冷冻肺组织的超薄冰冻切片进行免疫金标记。通过透射电子显微镜对肺泡内皮细胞和上皮细胞质膜上的金颗粒进行定量。在中性粒细胞向肺炎链球菌迁移（兔中一种不依赖CD18的途径）的过程中，毛细血管内皮ICAM-1表达没有变化。相反，对大肠杆菌内毒素（已知在小鼠中引发依赖CD18的迁移）的反应中，ICAM-1表达增加了4.2倍，这表明黏附机制可能受内皮而非中性粒细胞黏附分子表达的调节。肺泡上皮细胞上ICAM-1的组成性表达比毛细血管内皮细胞高22倍。上皮表达主要局限于I型肺泡上皮细胞，而I型细胞的前体细胞II型肺泡上皮细胞表达很少或不表达ICAM-1。然而，在肺炎期间，II型而非I型肺泡上皮细胞显示ICAM-1表达增加，这表明ICAM-1表达即使在对上皮损伤的反应中也代表一种早期分化。
