Hepatic leukostasis and hypoxic stress in adhesion molecule-deficient mice after gut ischemia/reperfusion.
Hepatic leukostasis and hypoxic stress in adhesion molecule-deficient mice after gut ischemia/reperfusion.
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肠道缺血/再灌注后粘附分子缺陷小鼠的肝白细胞停滞和缺氧应激。
DOI：
10.1172/jci119224
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Granger,DN
中科院分区：
文献类型：
--
作者：
Horie,Y;Wolf,R;Anderson,DC;Granger,DN
白细胞-内皮细胞粘附（LECA）是缺血/再灌注（I/R）引起的组织损伤的主要决定因素，这一概念主要是基于使用粘附分子特异性单克隆抗体的研究。本研究的目的是评估LECA对I/R损伤的贡献，使用细胞内粘附分子-1，P-选择素或CD 11/CD 18缺陷的突变小鼠（均为C57 B1背景）。释放阻塞（15分钟）的上级肠系膜动脉后1小时，通过活体显微镜监测对照和粘附分子缺陷小鼠肝脏中荧光标记白细胞的积聚和未灌注窦的数量。吡啶核苷酸（NADH）的自发荧光测定作为线粒体O2消耗和氧化还原状态的指标。与C57 B1（对照）小鼠的基线值相比，肠道I/R后肝脏中静止白细胞的数量显著升高。在这些小鼠中，尤其是在中央周围区，I/R后NADH的自体荧光也显著增加（指示缺氧）。相对于C57 B1小鼠，细胞间粘附分子-1-、CD 11/CD 18-和P-选择素缺陷小鼠均表现出对I/R的钝性白细胞隔离反应和非灌注窦的较小增量。所有的粘附分子缺陷小鼠也表现出衰减的增加，在中央周围区的NADH自发荧光，相对于对照小鼠。这些来自粘附分子缺陷小鼠的结果为LECA是肠I/R诱导的肝功能障碍的重要决定因素的观点提供了额外的支持。
The concept that leukocyte-endothelial cell adhesion (LECA) is a major determinant of the tissue injury elicited by ischemia/reperfusion (I/R) is largely based on studies employing adhesion molecule-specific monoclonal antibodies. The objective of this study was to assess the contribution of LECA to I/R injury using mutant mice (all on a C57B1 background) that are deficient in either intracellular adhesion molecule-1, P-selectin, or CD11/CD18. The accumulation of fluorescently labeled leukocytes and the number of nonperfused sinusoids in livers of control and adhesion molecule-deficient mice were monitored by intravital microscopy for 1 h after release of the occluded (for 15 min) superior mesenteric artery. Autofluorescence of pyridine nucleotide (NADH) was measured as an indicator of mitochondrial O2 consumption and redox status. The number of stationary leukocytes in the liver after gut I/R was significantly elevated compared with baseline values in C57B1 (control) mice. Autofluorescence of NADH was also significantly increased (indicating hypoxia) after I/R in these mice, especially in the pericentral region. Intercellular adhesion molecule-1-, CD11/CD18-, and P-selectin-deficient mice all exhibited a blunted leukosequestration response to I/R and smaller increments in nonperfused sinusoids, relative to C57B1 mice. All adhesion molecule-deficient mice also exhibited an attenuated increment in NADH autofluorescence in the pericentral region, relative to control mice. These results from adhesion molecule-deficient mice provide additional support for the view that LECA is an important determinant of the liver dysfunction induced by gut I/R.