ISCHEMIA INCREASES NEUTROPHIL RETENTION AND WORSENS ACUTE-RENAL-FAILURE - ROLE OF OXYGEN METABOLITES AND ICAM-1
ISCHEMIA INCREASES NEUTROPHIL RETENTION AND WORSENS ACUTE-RENAL-FAILURE - ROLE OF OXYGEN METABOLITES AND ICAM-1
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DOI：
10.1038/ki.1995.451
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发表时间：
1995-11-01
影响因子：
19.6
通讯作者：
REPINE, JE
中科院分区：
文献类型：
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作者：
LINAS, SL;WHITENBURG, D;REPINE, JE
中性粒细胞在急性肾衰竭（ARF）中的作用存在争议。尽管 ARF 发生在中性粒细胞减少的受试者中，但我们发现缺血肾脏激活中性粒细胞，从而在离体灌注大鼠肾脏中引起 ARF。为了进一步明确中性粒细胞和肾缺血之间的相互作用，我们对肾缺血期间中性粒细胞的积累进行了定量评估。通过离体肾脏技术，用未刺激的、引发的或完全激活的、铟标记的中性粒细胞对非缺血和缺血的大鼠肾脏进行灌注。通过测量灌注 60 分钟后的铟保留来定量中性粒细胞积累。在非缺血性肾脏中，仅保留活化的中性粒细胞，而肾缺血20分钟后，保留未刺激的以及活化的中性粒细胞。缺血 10 分钟后，激活的中性粒细胞（但不是未刺激的中性粒细胞）被保留。在中性粒细胞潴留的情况下，GFR 和肾小管钠重吸收降低。为了确定 ICAM 1 在缺血性损伤中的作用，在缺血前用抗 ICAM 1 治疗大鼠，并用未刺激的中性粒细胞和抗 ICAM 1 对缺血肾脏进行再灌注。缺血后，用抗 ICAM 1 预防离体肾脏再灌注损伤的中性粒细胞成分。氧代谢物已被证明可诱导 ICAM 1 的 EC 表达。为了确定 ICAM 1 在缺血性损伤中的作用。氧化剂介导的肾损伤，缺血的离体肾脏用过氧化氢酶（CAT）再灌注，非缺血的肾脏用过氧化氢灌注。缺血后，CAT 再灌注可防止中性粒细胞滞留和损伤。在非缺血性肾脏中，过氧化氢导致中性粒细胞滞留、活化和肾损伤，而抗ICAM 1可以完全预防这种情况。结论：（1）在离体肾脏中，缺血性肾脏导致中性粒细胞滞留、活化和肾损伤恶化； 2) 中性粒细胞滞留取决于中性粒细胞活化状态、肾缺血持续时间，并由氧代谢物和 ICAM 1 介导。这种协同作用可以解释脓毒症等同时存在肾脏灌注不足和中性粒细胞启动的情况下 ARF 的高频率。
The role of neutrophils in acute renal failure (ARF) is controversial. Although ARF occurs in neutropenic subjects, we found that ischemic kidneys activated neutrophils to cause ARF in isolated perfused rat kidneys. To further define the interaction between neutrophils and renal ischemia, we performed quantitative assessment of neutrophil accumulation during renal ischemia. Non-ischemic and ischemic rat kidneys were perfused by the isolated kidney technique with unstimulated, primed, or fully activated, indium-labeled neutrophils. Neutrophil accumulation was quantitated by measuring indium retention after 60 minutes of perfusion. In non-ischemic kidneys, only activated neutrophils were retained while after 20 minutes of renal ischemia, unstimulated as well as primed neutrophils were retained. Following 10 minutes of ischemia, primed neutrophils (but not unstimulated neutrophils) were retained. In the presence of neutrophil retention, there were decreases in GFR and tubular sodium reabsorption. To determine the role of ICAM 1 in ischemic injury, rats were treated with anti-ICAM 1 prior to ischemia and ischemic kidneys were reperfused with unstimulated neutrophils and anti-ICAM 1. After ischemia, the neutrophil component of reperfusion injury in isolated kidneys was prevented with anti-ICAM 1. Oxygen metabolites have been shown to induce EC expression of ICAM 1. To determine the role of ICAM 1 in oxidant-mediated renal injury, ischemic isolated kidneys were reperfused with catalase (CAT) and non-ischemic kidneys were perfused with hydrogen peroxide. Following ischemia, reperfusion with CAT prevented neutrophil retention and injury. In non-ischemic kidneys, hydrogen peroxide caused primed neutrophil retention, activation and renal injury which were completely prevented with anti-ICAM 1. In conclusion: (1) Ischemic kidneys cause neutrophil retention, activation, and worsening of renal injury in isolated kidneys; and 2) neutrophil retention is dependent on the state of neutrophil activation, duration of renal ischemia and is mediated by oxygen metabolites and ICAM 1. This synergism could account for the high frequency of ARF in conditions such as sepsis where there is both renal hypoperfusion and neutrophil priming.