针对细胞间黏附分子-1（ICAM-1）和淋巴细胞功能相关抗原-1（LFA-1）的抗体均不能保护肾脏免受毒性（氯化汞）损伤。

Antibodies to both ICAM-1 and LFA-1 do not protect the kidney against toxic (HgCl2) injury.

作者信息

Ghielli M, Verstrepen W A, De Greef K E, Helbert M H, Ysebaert D K, Nouwen E J, De Broe M E

机构信息

Department of Nephrology-Hypertension, University of Antwerp, Belgium.

出版信息

Kidney Int. 2000 Sep;58(3):1121-34. doi: 10.1046/j.1523-1755.2000.00269.x.

DOI:10.1046/j.1523-1755.2000.00269.x

PMID:10972676

Abstract

BACKGROUND

The role of inflammatory leukocytes in acute renal failure (ARF) remains controversial and appears largely uninvestigated in toxic (in contrast to ischemic) ARF.

METHODS

Female Wistar rats were injected with monoclonal antibodies (mAbs) directed to both the leukocyte function-associated antigen 1 (LFA-1) and the intercellular adhesion molecule 1 (ICAM-1). Doses (6 mg/kg of each mAb) were given 24 hours prior to the induction of acute tubular necrosis (ATN) by mercuric chloride administration (2 mg/kg, subcutaneously, day 0) and subsequently every 48 hours. Control rats similarly received either control antibody (12 mg/kg) or vehicle prior to and following the induction of ATN. Renal function was also measured from male Lewis rats that were similarly treated with anti-adhesion antibodies during exposure to 30 minutes of unilateral renal ischemia.

RESULTS

Injected antibodies were demonstrated on peripheral blood leukocytes (flow cytometrical detection of mouse anti-LFA-1) and on endothelium (immunohistochemical staining of mouse anti-ICAM-1) and were measured in serum (enzyme-linked immunosorbent assay). Macrophages and T cells were prominent in the kidney of control treatment rats after HgCl2 injection, but anti-adhesion treatment clearly had prevented their infiltration. Notwithstanding, renal tubular injury was equally pronounced in all mercuric chloride treatment groups and so was the decline in renal function (serum creatinine, proteinuria). Tubular epithelial cell proliferation seemed slightly less pronounced and delayed in anti-adhesion treated rats. Kidneys from ischemia exposed rats were, however, functionally protected by identical anti-ICAM-1/anti-LFA-1 treatment.

CONCLUSION

Prevention of cellular infiltration by mAbs to LFA-1 and ICAM-1 has no effect on renal morphology, function, or regeneration following mercuric chloride-induced ARF in the rat. This result contrasts with the functional protection of the rat kidney to ischemia/reperfusion injury by virtue of an identical antibody treatment protocol. Resolving that controversy should bring better insight in fundamental processes underlying different types of ARF, and will be the subject of further study.

摘要

背景

炎症性白细胞在急性肾衰竭（ARF）中的作用仍存在争议，并且在中毒性（与缺血性相对）急性肾衰竭中似乎很大程度上未得到研究。

方法

给雌性Wistar大鼠注射针对白细胞功能相关抗原1（LFA-1）和细胞间黏附分子1（ICAM-1）的单克隆抗体（mAb）。在通过给予氯化汞（2mg/kg，皮下注射，第0天）诱导急性肾小管坏死（ATN）前24小时给予剂量（每种mAb 6mg/kg），随后每48小时给药一次。对照大鼠在诱导ATN前后同样接受对照抗体（12mg/kg）或赋形剂。在雄性Lewis大鼠暴露于30分钟单侧肾缺血期间，用抗黏附抗体进行类似处理后，也对其肾功能进行了测量。

结果

在外周血白细胞上证实了注射的抗体（通过流式细胞术检测小鼠抗LFA-1）以及在内皮上（通过小鼠抗ICAM-1的免疫组织化学染色），并在血清中进行了测量（酶联免疫吸附测定）。注射氯化汞后，对照处理大鼠的肾脏中巨噬细胞和T细胞很突出，但抗黏附处理明显阻止了它们的浸润。尽管如此，在所有氯化汞处理组中肾小管损伤同样明显，肾功能下降（血清肌酐、蛋白尿）也是如此。在抗黏附处理的大鼠中，肾小管上皮细胞增殖似乎稍不明显且延迟。然而，缺血暴露大鼠的肾脏通过相同的抗ICAM-1/抗LFA-1处理在功能上得到了保护。