Lang Carol J, Barnett Emma K, Doyle Ian R
Department of Human Physiology, Flinders University of South Australia, Bedford Park, SA 5042, Australia.
Cytokine. 2006 Mar 21;33(6):346-51. doi: 10.1016/j.cyto.2006.03.006. Epub 2006 May 19.
Ventilatory-induced strain can exacerbate acute lung injury (ALI). Current ventilation strategies favour low tidal volumes and high end-expiratory volumes to 'rest' the lung, but can lead to an increase in CO2. Alveolar macrophages (AM) play a pivotal role in ALI through the release of inflammatory mediators. The effect of physical strain and CO2 on the release of pro-inflammatory mediators was examined in isolated rat AM. AM were cultured on IgG-coated silastic membranes with or without lipopolysaccharide (LPS) and 5% or 20% CO2 and subjected to a repetitive sinusoidal mechanical strain (30%, 60 cycles/min) for 4 h. Cell viability and metabolic activity were assessed. In both the presence and absence of LPS, physical strain increased metabolic activity by approximately 5%, while 20% CO2 decreased metabolic activity by approximately 40%. Twenty per cent CO2 decreased TNF-alpha secretion by approximately 45%, without affecting cell viability. Physical strain enhanced LPS-induced secretion of TNF-alpha by 1.5%, but not IL-6 or CINC-1. Hence, the effects of both CO2 and physical strain are mediated independently through changes in AM metabolic activity. Physical strain is not a major determinant of TNF-alpha, IL-6 or CINC-1 in AM. Our results confirm that high CO2 can lessen the TNF-alpha inflammatory response of AM.
通气诱导的应变会加重急性肺损伤（ALI）。目前的通气策略倾向于采用低潮气量和高呼气末容积来使肺“休息”，但这可能会导致二氧化碳增加。肺泡巨噬细胞（AM）通过释放炎症介质在ALI中起关键作用。我们在分离的大鼠AM中研究了物理应变和二氧化碳对促炎介质释放的影响。将AM培养在包被有IgG的硅橡胶膜上，分别给予脂多糖（LPS）和5%或20%的二氧化碳，并施加重复正弦机械应变（30%，60次/分钟）4小时。评估细胞活力和代谢活性。在有和没有LPS的情况下，物理应变均使代谢活性增加约5%，而20%的二氧化碳使代谢活性降低约40%。20%的二氧化碳使肿瘤坏死因子-α（TNF-α）分泌减少约45%，而不影响细胞活力。物理应变使LPS诱导的TNF-α分泌增加1.5%，但对白细胞介素-6（IL-6）或大鼠CXC趋化因子-1（CINC-1）没有影响。因此，二氧化碳和物理应变的作用都是通过AM代谢活性的变化独立介导的。物理应变不是AM中TNF-α、IL-6或CINC-1的主要决定因素。我们的结果证实，高二氧化碳可减轻AM的TNF-α炎症反应。
