Chen B, Keshive M, Deen W M
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA.
Biophys J. 1998 Aug;75(2):745-54. doi: 10.1016/S0006-3495(98)77564-2.
A reaction-diffusion model was developed to predict the fate of nitric oxide (NO) released by cells of the immune system. The model was used to analyze data obtained previously using macrophages attached to microcarrier beads suspended in a stirred vessel. Activated macrophages synthesize NO, which is oxidized in the culture medium by molecular oxygen and superoxide (O2-, also released by the cells), yielding mainly nitrite (NO2-) and nitrate (NO3-) as the respective end products. In the analysis the reactor was divided into a "stagnant film" with position-dependent concentrations adjacent to a representative carrier bead and a well-mixed bulk solution. It was found that the concentration of NO was relatively uniform in the film. In contrast, essentially all of the O2- was calculated to be consumed within approximately 2 microm of the cell surfaces, due to its reaction with NO to yield peroxynitrite. The decomposition of peroxynitrite caused its concentration to fall to nearly zero over a distance of approximately 30 microm from the cells. Although the film regions (which had an effective thickness of 63 microm) comprised just 2% of the reactor volume and were predicted to account for only 6% of the NO2- formation under control conditions, they were calculated to be responsible for 99% of the NO3- formation. Superoxide dismutase in the medium (at 3.2 microM) was predicted to lower the ratio of NO3- to NO2- formation rates from near unity to <0.5, in reasonable agreement with the data. The NO3-/NO2- ratio was predicted to vary exponentially with the ratio of O2- to NO release rates from the cells. Recently reported reactions involving CO2 and bicarbonate were found to have important effects on the concentrations of peroxynitrite and nitrous anhydride, two of the compounds that have been implicated in NO cytotoxicity and mutagenesis.
开发了一种反应扩散模型来预测免疫系统细胞释放的一氧化氮（NO）的归宿。该模型用于分析先前使用附着在悬浮于搅拌容器中的微载体珠上的巨噬细胞获得的数据。活化的巨噬细胞合成NO，NO在培养基中被分子氧和超氧化物（O2-，也由细胞释放）氧化，主要产生亚硝酸盐（NO2-）和硝酸盐（NO3-）作为各自的终产物。在分析中，反应器被分为一个“停滞膜”，其浓度随位置变化，紧邻一个代表性的载体珠，以及一个充分混合的主体溶液。发现NO在膜中的浓度相对均匀。相比之下，由于O2-与NO反应生成过氧亚硝酸根，计算得出基本上所有的O2-在细胞表面约2微米范围内被消耗。过氧亚硝酸根的分解导致其浓度在距细胞约30微米的距离内降至几乎为零。尽管膜区域（有效厚度为63微米）仅占反应器体积的2%，预计在对照条件下仅占NO2-形成的6%，但计算得出它们占NO3-形成的99%。培养基中的超氧化物歧化酶（浓度为3.2 microM）预计会将NO3-与NO2-形成速率的比值从接近1降至<0.5，这与数据合理相符。预计NO3-/NO2-比值会随细胞释放的O2-与NO速率的比值呈指数变化。发现最近报道的涉及CO2和碳酸氢盐的反应对过氧亚硝酸根和亚硝酸酐的浓度有重要影响，这两种化合物与NO的细胞毒性和诱变作用有关。
