The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia-reperfusion
The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia-reperfusion
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DOI：
10.4049/jimmunol.177.11.8080
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Austen, William G., Jr.
中科院分区：
文献类型：
--
作者：
Chan, Rodney K.;Ibrahim, Shahrul I.;Austen, William G., Jr.
补体是骨骼肌缺血再灌注损伤的重要介质。虽然经典途径被认为是导致损伤的主要激活途径，但甘露糖结合凝集素(MBL)途径也可能起到作用。在本研究中，我们发现，与野生型、经典途径特异性C1q缺陷小鼠或重组人MBL重组MBL缺陷小鼠相比，MBL缺陷小鼠在骨骼肌再灌注损伤后具有显著的保护作用。然而，MBL缺陷小鼠在缺血-再灌流后不能保护通透性水肿或继发性肺损伤。这些数据表明，单独阻断经典通路(C1q)对通透性、水肿和远端肺损伤具有保护作用，但对组织学肌肉损伤没有保护作用。相反，单独阻断MBL通路可预防组织学损伤，但不能预防通透性水肿或肺损伤。因此，这两条通路的激活很可能是骨骼肌再灌注损伤后观察到的全谱损伤的原因。
Complement is an important mediator of the injuries observed after skeletal muscle ischemia and subsequent reperfusion. Although the classical pathway had been assumed to be the major pathway of activation leading to injury, the mannose-binding lectin (MBL) pathway might also play a contributing role. In this study, we found that MBL-deficient mice had significant protection after skeletal muscle reperfusion injury compared with wild-type, classical pathway-specific C1q-deficient mice, or MBL-deficient mice reconstituted with recombinant human MBL. MBL-deficient mice, however, were not protected from permeability edema or secondary lung injury after ischemia-reperfusion. These data indicate that blockade of the classical pathway alone (C1q) is protective against permeability edema and remote pulmonary injury but not protective against histologic muscle injury. In contrast, blocking the MBL pathway alone protects against histological injury but is not protective against permeability edema or lung injury. Thus, the activation of both pathways is likely responsible for the full spectrum of injuries observed after skeletal muscle reperfusion injury.