细胞间黏附分子-1促进中性粒细胞介导的细胞毒性。

Intercellular adhesion molecule-1 promotes neutrophil-mediated cytotoxicity.

作者信息

Barnett C C, Moore E E, Moore F A, Biffl W L, Smith M F, Carl V S

机构信息

Department of Surgery, Denver General Hospital, Colo 80204, USA.

出版信息

Surgery. 1995 Aug;118(2):171-5; discussion 176. doi: 10.1016/s0039-6060(05)80320-4.

DOI:10.1016/s0039-6060(05)80320-4

PMID:7638730

Abstract

BACKGROUND

Interaction of the CD11/CD18 complex on polymorphonuclear neutrophils (PMNs) and intercellular adhesion molecule (ICAM)-1 on endothelium is a critical event in PMN-mediated tissue injury. In addition, increased expression of ICAM-1 on type I pneumocytes has been identified in a variety of pulmonary disorders associated with PMN-induced inflammation. We hypothesized that ICAM-1 up-regulation is sufficient to promote cytotoxicity via activated PMNs.

METHODS

The complementary DNA for human ICAM-1 was transfected into Chinese hamster ovarian (CHO) cells, which do not inherently express this adhesion receptor, by using the expression vector CD1.8. Fluorescence-activated cell sorter analysis revealed 62% CHO cell surface expression of ICAM-1. Wild type and transfected CHO cells were labeled with chromium 51 and exposed to quiescent or activated (1 mumol/L phorbol myristate acetate) PMNs for 4 hours. Subsets were pretreated with a monoclonal antibody to ICAM-1. PMN cytotoxicity was determined by specific percent 51Cr release.

RESULTS

Incubation of quiescent PMNs with wild type and transfected CHO cells produced nominal cell lysis, 0.5% +/- 0.3% and 0.2% +/- 0.2%, respectively. Activated PMNs produced 13.6% +/- 3.2% versus 1.4% +/- 0.7% cell lysis, comparing transfected with wild type CHO cells, and 0.5% +/- 0.2% cell lysis after pretreatment with a monoclonal antibody to ICAM-1, p < 0.01.

CONCLUSIONS

ICAM-1 up-regulation is sufficient to promote cytotoxicity via activated PMNs. This may represent a potential target for attenuating PMN-mediated injury to endothelial and other cell lines, including parenchyma.

摘要

背景

多形核中性粒细胞（PMN）上的CD11/CD18复合物与内皮细胞上的细胞间黏附分子（ICAM）-1相互作用是PMN介导的组织损伤中的关键事件。此外，在多种与PMN诱导的炎症相关的肺部疾病中，已发现I型肺细胞上ICAM-1的表达增加。我们假设ICAM-1的上调足以通过活化的PMN促进细胞毒性。

方法

使用表达载体CD1.8将人ICAM-1的互补DNA转染到天然不表达这种黏附受体的中国仓鼠卵巢（CHO）细胞中。荧光激活细胞分选分析显示ICAM-1在CHO细胞表面的表达率为62%。野生型和转染的CHO细胞用51铬标记，并与静止或活化的（1μmol/L佛波酯肉豆蔻酸酯）PMN接触4小时。部分细胞用抗ICAM-1单克隆抗体预处理。通过51铬特异性释放百分比来测定PMN细胞毒性。

结果

静止的PMN与野生型和转染的CHO细胞孵育产生的细胞裂解率很低，分别为0.5%±0.3%和0.2%±0.2%。与野生型CHO细胞相比，活化的PMN对转染的CHO细胞产生的细胞裂解率为13.6%±3.2%，而对野生型CHO细胞为1.4%±0.7%，用抗ICAM-1单克隆抗体预处理后细胞裂解率为0.5%±0.2%，p<0.01。