Cale A R, Katzmann J A, Tazelaar H D, Miller V M, McGregor C G
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minn.
J Heart Lung Transplant. 1993 Nov-Dec;12(6 Pt 1):948-54; discussion 955.
Monoclonal antibodies against leukocyte adhesion molecules reduce the severity of reperfusion injury and, in some cases, prevent acute allograft rejection. These effects are assumed to be due to prevention of leukocyte-endothelial adhesion. Experiments were designed to study activation of polymorphonuclear leukocytes during acute rejection of canine single lung allografts and to test the ability of an anti-beta 2-integrin monoclonal antibody (R15.7/H4) to regulate leukocyte metabolism independent of leukocyte-endothelial adhesion. Peripheral blood polymorphonuclear leukocytes were obtained by Ficoll-Hypaque centrifugation from unoperated control dogs (n = 10), from dogs with a single lung autotransplant (n = 4), and from dogs after single lung allotransplantation during unmodified rejection (n = 12). Oxygen radicals were measured with luminal-enhanced chemiluminescence of unstimulated polymorphonuclear leukocytes, polymorphonuclear leukocytes stimulated by opsonized-zymosan, and polymorphonuclear leukocytes incubated with anti-beta 2-integrin beta-chain (CD18) monoclonal antibodies before exposure to opsonized zymosan. Polymorphonuclear leukocyte viability was unaffected by the monoclonal antibodies. Polymorphonuclear leukocytes from unoperated and autotransplant dogs did not produce oxygen radicals unless stimulated by opsonized zymosan. Polymorphonuclear leukocytes from rejecting animals produced oxygen radicals in the absence of zymosan, and when stimulated, production of oxygen radicals was significantly greater than that of polymorphonuclear leukocytes from unoperated and autotransplant dogs. Production of oxygen radicals was inhibited significantly by the monoclonal antibodies in polymorphonuclear leukocytes from all three groups. This study shows that rejection activates polymorphonuclear leukocytes and increases the potential to produce activated oxygen species. In addition to inhibiting leukocyte adhesion to endothelial cells, anti-beta 2-integrin monoclonal antibodies appears to suppress production of oxygen radicals by polymorphonuclear leukocytes.
抗白细胞黏附分子的单克隆抗体可减轻再灌注损伤的严重程度，在某些情况下还可预防急性移植排斥反应。这些作用被认为是由于阻止了白细胞与内皮细胞的黏附。本实验旨在研究犬单肺同种异体移植急性排斥反应期间多形核白细胞的激活情况，并测试抗β2整合素单克隆抗体（R15.7/H4）在不依赖白细胞与内皮细胞黏附的情况下调节白细胞代谢的能力。通过Ficoll-Hypaque离心法从未手术的对照犬（n = 10）、单肺自体移植犬（n = 4）以及单肺同种异体移植后处于未改良排斥反应期的犬（n = 12）获取外周血多形核白细胞。采用未刺激的多形核白细胞、经调理酵母聚糖刺激的多形核白细胞以及在暴露于调理酵母聚糖之前与抗β2整合素β链（CD18）单克隆抗体孵育的多形核白细胞的腔内增强化学发光法来测定氧自由基。单克隆抗体未影响多形核白细胞的活力。未手术和自体移植犬的多形核白细胞在未受调理酵母聚糖刺激时不产生氧自由基。来自排斥动物的多形核白细胞在无酵母聚糖的情况下产生氧自由基，并且在受到刺激时，其氧自由基的产生量显著高于未手术和自体移植犬的多形核白细胞。三组多形核白细胞中的氧自由基产生均被单克隆抗体显著抑制。本研究表明，排斥反应激活了多形核白细胞并增加了产生活性氧的潜力。除了抑制白细胞与内皮细胞的黏附外，抗β2整合素单克隆抗体似乎还能抑制多形核白细胞产生氧自由基。
