Hobden Jeffrey A
Department of Immunology/Microbiology, Wayne State University, School of Medicine, Detroit, Michigan 48201, USA.
DNA Cell Biol. 2003 Oct;22(10):649-55. doi: 10.1089/104454903770238120.
In a previous study, ICAM-1-deficient knockout (KO) mice were able to recruit inflammatory cells into Pseudomonas aeruginosa-infected eyes and resolve the infection as well as wild-type (WT) mice. Based on this observation, it was hypothesized that ICAM-2 could serve as a surrogate receptor for leukocyte recruitment in lieu of ICAM-1. To test this hypothesis, ICAM-2 expression was first examined in both uninfected and P. aeruginosa-infected eyes (6 h postinfection) by immunohistochemistry and RT-PCR. Similar to ICAM-1, ICAM-2 was constitutively expressed on the vascular endothelium of the iris, ciliary body, and conjunctiva of uninfected eyes. Unlike ICAM-1, ICAM-2 was not expressed in the cornea nor upregulated following P. aeruginosa infection. The role of ICAM-2 in P. aeruginosa ocular infection was then addressed through a monoclonal antibody (MAb) blockade of ICAM-2 in infected ICAM-1 KO and WT mice. MAb blockade of ICAM-2 resulted in fewer infiltrating inflammatory cells (as ascertained by histopathology) in the anterior chamber of eyes of ICAM-1-KO and WT mice 24 h postinfection. However, a myeloperoxidase assay of infected corneas showed no statistical difference (P > 0.11) between the two groups in infiltrating PMN. Collectively, these data suggest that constitutively expressed ICAM-2 does play a role in recruiting inflammatory cells into the anterior chamber of the eye during P. aeruginosa infection. Furthermore, inflammatory cell recruitment into the P. aeruginosa-infected cornea appears to be mediated by an ICAM-independent pathway.
在先前的一项研究中，ICAM - 1基因敲除（KO）小鼠能够将炎性细胞募集到感染铜绿假单胞菌的眼中，并像野生型（WT）小鼠一样清除感染。基于这一观察结果，研究人员推测ICAM - 2可以作为替代受体，代替ICAM - 1介导白细胞募集。为了验证这一假设，首先通过免疫组织化学和逆转录 - 聚合酶链反应（RT - PCR）检测了未感染和感染铜绿假单胞菌（感染后6小时）的眼睛中ICAM - 2的表达情况。与ICAM - 1相似，ICAM - 2在未感染眼睛的虹膜、睫状体和结膜的血管内皮细胞上组成性表达。与ICAM - 1不同的是，ICAM - 2在角膜中不表达，在铜绿假单胞菌感染后也不会上调。随后，通过对感染的ICAM - 1基因敲除小鼠和野生型小鼠进行ICAM - 2单克隆抗体（MAb）阻断，研究了ICAM - 2在铜绿假单胞菌眼部感染中的作用。感染后24小时，对ICAM - 1基因敲除小鼠和野生型小鼠的眼睛前房进行MAb阻断ICAM - 2处理，结果显示浸润的炎性细胞数量减少（通过组织病理学确定）。然而，对感染角膜进行髓过氧化物酶检测发现，两组间浸润的中性粒细胞没有统计学差异（P > 0.11）。总体而言，这些数据表明，组成性表达的ICAM - 2在铜绿假单胞菌感染期间确实在将炎性细胞募集到眼前房中发挥作用。此外，炎性细胞募集到感染铜绿假单胞菌的角膜似乎是由一条不依赖ICAM的途径介导的。
