Gonzalo J A, Pan Y, Lloyd C M, Jia G Q, Yu G, Dussault B, Powers C A, Proudfoot A E, Coyle A J, Gearing D, Gutierrez-Ramos J C
Millennium Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
J Immunol. 1999 Jul 1;163(1):403-11.
The cloning, expression, and function of the murine (m) homologue of human (h) monocyte-derived chemokine (MDC) is reported here. Like hMDC, mMDC is able to elicit the chemotactic migration in vitro of activated lymphocytes and monocytes. Among activated lymphocytes, Th2 cells were induced to migrate most efficiently. mMDC mRNA and protein expression is modulated during the course of an allergic reaction in the lung. Neutralization of mMDC with specific Abs in a model of lung inflammation resulted in prevention of airway hyperreactivity and significant reduction of eosinophils in the lung interstitium but not in the airway lumen. These data suggest that mMDC is essential in the transit/retention of leukocytes in the lung tissue rather than in their extravasation from the blood vessel or during their transepithelial migration into the airways. These results also highlight the relevance of factors, such as mMDC, that regulate the migration and accumulation of leukocytes within the tissue during the development of the key physiological endpoint of asthma, airway hyperreactivity.
本文报道了人单核细胞衍生趋化因子（MDC）的小鼠（m）同源物的克隆、表达及功能。与hMDC一样，mMDC能够在体外引发活化淋巴细胞和单核细胞的趋化迁移。在活化淋巴细胞中，Th2细胞被诱导迁移的效率最高。在肺部过敏反应过程中，mMDC的mRNA和蛋白表达受到调节。在肺部炎症模型中，用特异性抗体中和mMDC可预防气道高反应性，并显著减少肺间质而非气道腔内的嗜酸性粒细胞。这些数据表明，mMDC对于白细胞在肺组织中的转运/滞留至关重要，而非在其从血管渗出或经上皮迁移至气道的过程中起作用。这些结果还突出了诸如mMDC等因子在哮喘关键生理终点气道高反应性发展过程中调节白细胞在组织内迁移和聚集的相关性。
