ANTIBODY TO INTERCELLULAR-ADHESION MOLECULE-1 PROTECTS THE KIDNEY AGAINST ISCHEMIC-INJURY
ANTIBODY TO INTERCELLULAR-ADHESION MOLECULE-1 PROTECTS THE KIDNEY AGAINST ISCHEMIC-INJURY
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DOI：
10.1073/pnas.91.2.812
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发表时间：
1994-01-18
影响因子：
11.1
通讯作者：
BONVENTRE, JV
中科院分区：
文献类型：
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作者：
KELLY, KJ;WILLIAMS, WW;BONVENTRE, JV
缺血性急性肾功能衰竭的病理生理机制复杂，白细胞黏附在这一过程中的作用尚不清楚。抗细胞间黏附分子-1(抗ICAM-1)的单抗在大鼠双侧肾缺血时应用，可预防急性肾功能衰竭的功能损害和组织学改变。在缺血30min后24小时测得的血肌酐(mg/dl)，抗ICAM-1治疗组为0.61+/-0.05，而赋形剂治疗组为2.4+/-0.14(P<；0.0001)。缺血48h，抗细胞间黏附分子-1抗体和赋形剂治疗组的肌酸值分别为0.46+/-0.05和2.03+/-0.22(P<；0.0001)。小剂量的抗ICAM-1本身是非保护性的，当给予部分保护性剂量的抗淋巴细胞功能相关抗原-1的单抗(抗-LFA-1)时，对预防肾功能衰竭起协同作用。抗ICAM-1单抗在血流恢复后0.5小时或2小时给药时对肾脏有保护作用，而在血流恢复后8小时给药对肾脏无保护作用。抗ICAM-1治疗减轻了缺血引起的组织髓过氧化物酶的增加，髓过氧化物酶是中性粒细胞渗透的标志。因此，即使在缺血期后给予抗体，抗ICAM-1单抗也能保护肾脏免受缺血性肾功能衰竭的影响。这些结果表明白细胞和黏附分子在缺血性损伤的病理生理学中起着关键作用，并可能具有重要的治疗意义。
The pathophysiology of ischemic acute renal failure is complex, and the role of leukocyte adhesion in this process is not well defined. A monoclonal antibody (mAb) against intracellular adhesion molecule 1 (anti-ICAM-1), administered at the time of bilateral renal ischemia in the rat, prevented both functional impairment and histologic changes of acute renal failure. Plasma creatinine measured (mg/dl) 24 hr after 30 min of ischemia was 0.61 +/- 0.05 in the anti-ICAM-1-treated animals compared with 2.4 +/- 0.14 (P < 0.0001) in the vehicle-treated ischemic group. Forty-eight hours after ischemia, creatinine values were 0.46 +/- 0.05 and 2.03 +/- 0.22 (P < 0.0001) in anti-ICAM-1 and vehicle-treated groups, respectively. A low dose of anti-ICAM-1 that was itself nonprotective, when given with partially protective doses of a mAb against lymphocyte function-associated antigen-1 (anti-LFA-1), acted synergistically to prevent renal failure. Anti-ICAM-1 mAb also protected the kidney when administered 0.5 or 2 hr but not 8 hr after restoration of blood flow and when the ischemic period was extended to 40 min. Ischemia-induced increases in tissue myeloperoxidase, a marker of neutrophil infiltration, were mitigated with anti-ICAM-1 treatment. Thus, anti-ICAM-1 mAb protected the kidney against ischemic renal failure, even when the antibody was administered after the ischemic period. These results suggest a critical role for leukocytes and adhesion molecules in the pathophysiology of ischemic injury and may have important therapeutic implications.