An agent-based model of inflammation and fibrosis following particulate exposure in the lung.
An agent-based model of inflammation and fibrosis following particulate exposure in the lung.
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DOI：
10.1016/j.mbs.2011.03.005
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发表时间：
2011-06
影响因子：
4.3
通讯作者：
Vodovotz Y
中科院分区：
文献类型：
--
作者：
Brown BN;Price IM;Toapanta FR;DeAlmeida DR;Wiley CA;Ross TM;Oury TD;Vodovotz Y
炎症和气道重塑发生在多种气道疾病中。对反复暴露于颗粒物后的炎症和纤维化过程进行建模，可以为了解气道疾病的频谱以及预防/治疗策略提供见解。我们建立了一个基于药物的模型（ABM）来检测提取的炎症细胞（名义上是巨噬细胞，但可能包括其他炎症细胞，如淋巴细胞）和参与重塑的细胞（名义上是成纤维细胞）对颗粒暴露的反应。该模型专注于有限数量的相关相互作用，特别是巨噬细胞、成纤维细胞、促炎细胞因子（TNF-α）、抗炎细胞因子（TGF-β1）、胶原沉积和组织损伤之间的相互作用。该模型产生了三种不同的状态，等同于(1)自解炎症并恢复到基线，(2)局部组织损伤和纤维化的促炎过程，以及(3)促炎和抗炎细胞因子升高，持续组织损伤和纤维化结果。在暴露于颗粒物质的小鼠肺组织的组织学切片中观察到与这些预测状态一致的实验结果。系统的计算机研究表明，每种状态的发展主要取决于暴露的程度和持续时间。因此，一个相对简单的ABM导致了几种生物学上可行的紧急状态，这表明该模型捕捉到了肺部暴露于颗粒物后炎症的某些显著特征。这种ABM可能在微粒暴露后由炎症和纤维化引起的气道疾病中具有未来的实用性。
Inflammation and airway remodeling occur in a variety of airway diseases. Modeling aspects of the inflammatory and fibrotic processes following repeated exposure to particulate matter may provide insights into a spectrum of airway diseases, as well as prevention/treatment strategies. An agent-based model (ABM) was created to examine the response of an abstracted population of inflammatory cells (nominally macrophages, but possibly including other inflammatory cells such as lymphocytes) and cells involved in remodeling (nominally fibroblasts) to particulate exposure. The model focused on a limited number of relevant interactions, specifically those among macrophages, fibroblasts, a pro-inflammatory cytokine (TNF-α), an anti-inflammatory cytokine (TGF-β1), collagen deposition, and tissue damage. The model yielded three distinct states that were equated with (1) self-resolving inflammation and a return to baseline, (2) a pro-inflammatory process of localized tissue damage and fibrosis, and (3) elevated pro- and anti-inflammatory cytokines, persistent tissue damage, and fibrosis outcomes. Experimental results consistent with these predicted states were observed in histology sections of lung tissue from mice exposed to particulate matter. Systematic in silico studies suggested that the development of each state depended primarily upon the degree and duration of exposure. Thus, a relatively simple ABM resulted in several, biologically feasible, emergent states, suggesting that the model captures certain salient features of inflammation following exposure of the lung to particulate matter. This ABM may hold future utility in the setting of airway disease resulting from inflammation and fibrosis following particulate exposure.
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DOI：
10.1164/ajrccm.158.6.9803053
发表时间：
1998-12-01
影响因子：
24.7
作者：
de Boer, WI;van Schadewijk, A;van Krieken, JHJM
通讯作者：
van Krieken, JHJM
影响因子：
14.2
作者：
Alexis, NE;Lay, JC;Becker, S
通讯作者：
Becker, S
影响因子：
5.8
作者：
Aldonyte, R;Jansson, L;Janciauskiene, S
通讯作者：
Janciauskiene, S
影响因子：
1.4
作者：
An, Gary;Faeder, James;Vodovotz, Yoram
通讯作者：
Vodovotz, Yoram
影响因子：
5.6
作者：
Fraig, M;Shreesha, U;Katzenstein, ALA
通讯作者：
Katzenstein, ALA