Haslett C, Savill J S, Meagher L
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Curr Opin Immunol. 1989 Oct;2(1):10-8. doi: 10.1016/0952-7915(89)90091-5.
In 'beneficial inflammation', which is the major component of our innate immune system, it is possible to predict an 'ideal' sequence of cellular events: neutrophil migration would be rapid; time of contact with endothelial cells minimized; matrix degradation localized, with specific turn-on and turn-off of degradation mechanisms; neutrophil secretion and disintegration would be kept to a minimum during bacterial killing; and finally, rapid cessation of neutrophil migration and rapid removal of intact senescent cells would occur. Any doubts that the cellular events of the early stages of acute inflammation normally involve highly sophisticated cellular interactions, presumably designed to minimize tissue perturbation, should be dispelled by two elegant recent studies of neutrophil-endothelial interaction. Clearly, defects in the control of these processes could tip the balance towards cell injury or excessive matrix degradation and initiate amplification mechanisms leading to persistent inflammation and disease. The further identification of molecular mechanisms of these events should permit specific intervention in neutrophil-mediated disease. However, it is important to remember, firstly, that the neutrophil is just a part of the highly redundant inflammatory process and the removal of one 'strand' does not mean that the whole 'web' breaks down, and secondly, that impairment of neutrophil mechanisms may critically impair our anti-bacterial defences. Therefore, continued attempts should be made to define how cells and mediators interact in concert, to determine the fine specificity of molecular mechanisms and, in parallel, to identify 'time windows' in diseases, during which these mechanisms are more critical to the processes damaging the host than they are essential to its defences.
在作为我们固有免疫系统主要组成部分的“有益炎症”中，可以预测细胞事件的“理想”序列：中性粒细胞迁移迅速；与内皮细胞的接触时间最短；基质降解局限化，降解机制有特定的开启和关闭；在细菌杀灭过程中，中性粒细胞的分泌和崩解应保持在最低限度；最后，中性粒细胞迁移迅速停止，完整的衰老细胞迅速清除。近期两项关于中性粒细胞与内皮细胞相互作用的出色研究应该可以消除任何疑虑，即急性炎症早期阶段的细胞事件通常涉及高度复杂的细胞相互作用，大概是为了尽量减少组织扰动而设计的。显然，这些过程控制方面的缺陷可能会使平衡向细胞损伤或过度基质降解倾斜，并启动导致持续性炎症和疾病的放大机制。对这些事件分子机制的进一步识别应该能够对中性粒细胞介导的疾病进行特异性干预。然而，重要的是要记住，首先，中性粒细胞只是高度冗余的炎症过程的一部分，去除一条“线”并不意味着整个“网”会崩溃，其次，中性粒细胞机制的受损可能会严重损害我们的抗菌防御能力。因此，应该继续努力确定细胞和介质如何协同相互作用，确定分子机制的精细特异性，同时，确定疾病中的“时间窗”，在这些时间窗内，这些机制对损害宿主的过程比其对宿主防御的重要性更为关键。
