The role of ICAM-1 in endotoxin-induced acute renal failure
2007; American Physical Society; Volume: 293; Issue: 4 Linguagem: Inglês
10.1152/ajprenal.00445.2006
ISSN1931-857X
AutoresXiaoyan Wu, Rongqing Guo, Ying Wang, Patrick N. Cunningham,
Tópico(s)Neutrophil, Myeloperoxidase and Oxidative Mechanisms
ResumoThe pathogenesis of acute renal failure (ARF) occurring during the course of sepsis is incompletely understood. Intercellular adhesion molecule-1 (ICAM-1) is a key cell adhesion molecule upregulated by LPS, which binds to the integrins CD11a/CD18 and CD11b/CD18 present on the surface of leukocytes. We hypothesized that ICAM-1 facilitates renal injury in LPS-induced ARF. To test this, three groups of mice (n = 8 per group) were injected intraperitoneally with 6 mg/kg LPS: 1) normal C57BL/6 mice, 2) mice with a targeted deficiency of ICAM-1 (ICAM-1(-/-)), and 3) mice expressing very low levels of CD18 (CD18-def). ICAM-1(-/-) mice were significantly resistant to LPS-mediated ARF, as opposed to CD18-def mice, which developed severe ARF, as did wild-type controls (48 h blood urea nitrogen 143 +/- 31.5, 70.8 +/- 24.4, and 185 +/- 16.6 mg/dl in wild-type, ICAM-1(-/-), and CD18-def mice, respectively, P < 0.05). At death, ICAM-1(-/-) mice had significantly less renal neutrophil infiltration than the other two groups, as well as less histological tubular injury. Depletion of neutrophils with mAb Gr-1 led to a profound exaggeration of tumor necrosis factor (TNF) release and high mortality, but neutrophil-depleted mice receiving 10-fold less LPS were protected against ARF despite TNF release similar to what is normally associated with LPS-induced ARF. LPS caused a significant increase in renal expression of chemokines; however, this increase was significantly exaggerated in CD18-def mice, which may account for their lack of protection. In conclusion, these data show that ICAM-1 plays a key role in LPS-induced ARF.
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