Li X C, Miyasaka M, Issekutz T B
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
J Immunol. 1998 Dec 1;161(11):6258-64.
In acute lung inflammation, blood neutrophils and monocytes migrate into the lung parenchyma and bronchoalveolar space. The infiltration of the inflamed lung by monocytes is poorly understood because of difficulties in quantifying these cells in the presence of resident macrophages. Radiolabeled monocytes were used to study monocyte migration into the inflamed rat lung. Monocytes and neutrophils were purified from blood, labeled with 51Cr and (111)In, respectively, and injected i.v. into rats given an intratracheal injection of LPS. The accumulation of 51Cr-labeled monocytes increased > 10-fold in the lung parenchyma and 170-fold in the bronchoalveolar lavage (BAL) 18 h after LPS. (111)In-labeled neutrophils increased > 30-fold in the lung tissue and 500-fold in the BAL. Treatment of rats with a blocking anti-CD18 mAb inhibited monocyte accumulation in the lung and BAL by about 30%, whereas blocking very late activation Ag-4 (VLA-4) had no effect. Combined blockade of VLA-4 and CD18 inhibited approximately 30% of the migration to the lung parenchyma, but decreased the BAL by 80%. Monocyte migration to cutaneous inflammation was completely abolished by the combined mAb treatment. Neutrophil accumulation in the lung and BAL was not decreased by blocking either CD18 or VLA-4 and was only partially reduced by blocking CD18 plus VLA-4. Thus, monocyte migration to the LPS inflamed lung is substantially CD11/CD18 and VLA-4 independent, but accumulation in BAL is mediated by CD18 and VLA-4. Monocytes as well as neutrophils may use a previously unrecognized endothelial adhesion and migration pathway in the lung.
在急性肺部炎症中，血液中的中性粒细胞和单核细胞迁移至肺实质和支气管肺泡腔。由于在存在驻留巨噬细胞的情况下难以对这些细胞进行定量，单核细胞对炎症肺部的浸润情况尚不清楚。放射性标记的单核细胞被用于研究单核细胞向炎症大鼠肺部的迁移。单核细胞和中性粒细胞从血液中分离出来，分别用51Cr和（111）In标记，然后静脉注射到经气管内注射脂多糖（LPS）的大鼠体内。脂多糖注射18小时后，51Cr标记的单核细胞在肺实质中的蓄积增加了10倍以上，在支气管肺泡灌洗（BAL）液中增加了170倍。（111）In标记的中性粒细胞在肺组织中增加了30倍以上，在BAL液中增加了500倍。用阻断性抗CD18单克隆抗体治疗大鼠可使肺部和BAL液中的单核细胞蓄积减少约30%，而阻断极晚期活化抗原-4（VLA-4）则无作用。联合阻断VLA-4和CD18可抑制约30%的细胞向肺实质的迁移，但使BAL液中的细胞减少80%。联合单克隆抗体治疗可完全消除单核细胞向皮肤炎症部位的迁移。阻断CD18或VLA-4并不会减少中性粒细胞在肺部和BAL液中的蓄积，联合阻断CD18加VLA-4仅使其部分减少。因此，单核细胞向LPS炎症肺部的迁移在很大程度上不依赖CD11/CD18和VLA-4，但在BAL液中的蓄积是由CD18和VLA-4介导的。单核细胞和中性粒细胞可能在肺部利用了一种以前未被认识的内皮细胞黏附和迁移途径。
