Ishii Hiroshi, Hayashi Shizu, Hogg James C, Fujii Takeshi, Goto Yukinobu, Sakamoto Noriho, Mukae Hiroshi, Vincent Renaud, van Eeden Stephan F
James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, University of British Columbia, Vancouver, BC, V6Z 1Y6, Canada.
Respir Res. 2005 Aug 1;6(1):87. doi: 10.1186/1465-9921-6-87.
Studies from our laboratory have shown that human alveolar macrophages (AM) and bronchial epithelial cells (HBEC) exposed to ambient particles (PM10) in vitro increase their production of inflammatory mediators and that supernatants from PM10-exposed cells shorten the transit time of monocytes through the bone marrow and promote their release into the circulation.
The present study concerns co-culture of AM and HBEC exposed to PM10 (EHC-93) and the production of mediators involved in monocyte kinetics measured at both the mRNA and protein levels. The experiments were also designed to determine the role of the adhesive interaction between these cells via the intercellular adhesion molecule (ICAM)-1 in the production of these mediators.
AM/HBEC co-cultures exposed to 100 microg/ml of PM10 for 2 or 24 h increased their levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, macrophage inflammatory protein (MIP)-1beta, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6 and ICAM-1 mRNA, compared to exposed AM or HBEC mono-cultures, or control non-exposed co-cultures. The levels of GM-CSF, M-CSF, MIP-1beta and IL-6 increased in co-cultured supernatants collected after 24 h exposure compared to control cells (p < 0.05). There was synergy between AM and HBEC in the production of GM-CSF, MIP-1beta and IL-6. But neither pretreatment of HBEC with blocking antibodies against ICAM-1 nor cross-linking of ICAM-1 on HBEC blocked the PM10-induced increase in co-culture mRNA expression.
We conclude that an ICAM-1 independent interaction between AM and HBEC, lung cells that process inhaled particles, increases the production and release of mediators that enhance bone marrow turnover of monocytes and their recruitment into tissues. We speculate that this interaction amplifies PM10-induced lung inflammation and contributes to both the pulmonary and systemic morbidity associated with exposure to air pollution.
我们实验室的研究表明，体外暴露于环境颗粒物（PM10）的人肺泡巨噬细胞（AM）和支气管上皮细胞（HBEC）会增加其炎症介质的产生，并且来自暴露于PM10的细胞的上清液会缩短单核细胞通过骨髓的转运时间并促进其释放到循环中。
本研究涉及暴露于PM10（EHC-93）的AM和HBEC的共培养以及在mRNA和蛋白质水平上测量的参与单核细胞动力学的介质的产生。实验还旨在确定这些细胞之间通过细胞间粘附分子（ICAM）-1的粘附相互作用在这些介质产生中的作用。
与暴露的AM或HBEC单培养物或未暴露的对照共培养物相比，暴露于100μg/ml PM10 2小时或24小时的AM/HBEC共培养物增加了粒细胞-巨噬细胞集落刺激因子（GM-CSF）、M-CSF、巨噬细胞炎性蛋白（MIP）-1β、单核细胞趋化蛋白（MCP）-1、白细胞介素（IL）-6和ICAM-1 mRNA的水平。与对照细胞相比，暴露24小时后收集的共培养上清液中GM-CSF、M-CSF、MIP-1β和IL-6的水平增加（p<0.05）。AM和HBEC在GM-CSF、MIP-1β和IL-6的产生中存在协同作用。但是，用抗ICAM-1阻断抗体预处理HBEC或在HBEC上交联ICAM-1均不能阻断PM10诱导的共培养mRNA表达增加。
我们得出结论，处理吸入颗粒的肺细胞AM和HBEC之间的ICAM-1非依赖性相互作用增加了介质的产生和释放，这些介质增强了单核细胞的骨髓更新及其向组织中的募集。我们推测这种相互作用会放大PM10诱导的肺部炎症，并导致与空气污染暴露相关的肺部和全身发病率。
