Légaré Jean-Francois, Oxner Adam, Heimrath Olivier, Issekutz Thomas
Department of Surgery, Dalhousie University, Halifax, NS, Canada.
Int J Exp Pathol. 2007 Aug;88(4):291-300. doi: 10.1111/j.1365-2613.2007.00541.x.
Polymorphonuclear cells (PMN) are believed to be important effector cells responsible the myocardial damage seen following ischaemia. However, the exact kinetics of their migration remains controversial. Isolated PMN (10 x 10(6) cells) labelled with (51)Cr were injected into four groups of Lewis rats: 0 h (T0h; n = 13), 2 h (T2h; n = 7), 4 h (T4h; n = 7) or 6 h following ischaemia (T6h; n = 4). In all recipients, a left thoracotomy and ligation of the left anterior descending coronary was performed. Control animals underwent sham thoracotomy (n = 10). All animals were killed at 24 h and the radioactivity in the tissue measured to estimate labelled PMN migration. Monoclonal antibody blockade was also performed in experimental animals to assess the contribution of beta2 and alpha4 integrins to the PMN migration (n = 32). Labelled PMN migration to the myocardium was similar in all experimental groups, T0-T6h (7.2-11 x 10(5) labelled PMN) and significantly higher than sham controls (2.2 x 10(5) labelled PMN; P = 0.03). In contrast PMN migration to dermal inflammatory sites was highest in T0h group, and reached background level in the T4h and T6h groups. beta2 integrin blockade inhibited labelled PMN migration by 32%. Blockade of alpha4 integrin inhibited PMN migration by 30% while the combined beta2 + alpha4 blockade resulted in 63% inhibition of labelled PMN migration compared to treatment with isotype control antibody (P = 0.035). PMN migration following myocardial ischaemia persists over several hours after myocardial infarction and does not follow similar migration kinetics to dermal inflammation. Our findings also suggest that PMN migration is dependent equally on beta2 and alpha4 integrins.
多形核细胞（PMN）被认为是导致缺血后心肌损伤的重要效应细胞。然而，它们迁移的确切动力学仍存在争议。将用（51）铬标记的分离的PMN（10×10⁶个细胞）注射到四组Lewis大鼠中：缺血后0小时（T0h；n = 13）、2小时（T2h；n = 7）、4小时（T4h；n = 7）或6小时（T6h；n = 4）。在所有接受者中，进行左胸切开术并结扎左冠状动脉前降支。对照动物接受假胸切开术（n = 10）。所有动物在24小时处死，并测量组织中的放射性以估计标记的PMN迁移。还在实验动物中进行单克隆抗体阻断，以评估β2和α4整合素对PMN迁移的作用（n = 32）。在所有实验组T0 - T6h中，标记的PMN向心肌的迁移相似（7.2 - 11×10⁵个标记的PMN），且显著高于假手术对照组（2.2×10⁵个标记的PMN；P = 0.03）。相比之下，PMN向皮肤炎症部位的迁移在T0h组中最高，在T4h和T6h组中达到背景水平。β2整合素阻断使标记的PMN迁移减少32%。α4整合素阻断使PMN迁移减少30%，而β2 + α4联合阻断导致标记的PMN迁移比用同型对照抗体治疗减少63%（P = 0.035）。心肌缺血后的PMN迁移在心肌梗死后持续数小时，并且与皮肤炎症的迁移动力学不同。我们的研究结果还表明，PMN迁移同样依赖于β2和α4整合素。
