Abonia J Pablo, Hallgren Jenny, Jones Tatiana, Shi Tong, Xu Yuhui, Koni Pandelakis, Flavell Richard A, Boyce Joshua A, Austen K Frank, Gurish Michael F
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Smith Building, Room 624, 1 Jimmy Fund Way, Boston, MA 02115, USA.
Blood. 2006 Sep 1;108(5):1588-94. doi: 10.1182/blood-2005-12-012781. Epub 2006 May 2.
Normal mouse lungs lack appreciable numbers of mast cells (MCs) or MC progenitors (MCp's), yet the appearance of mature MCs in the tracheobronchial epithelial surface is a characteristic of allergic, T-cell-dependent pulmonary inflammation. We hypothesized that pulmonary inflammation would recruit MCp's to inflamed lungs and that this recruitment would be regulated by distinct adhesion pathways. Ovalbumin-sensitized and challenged mice had a greater than 28-fold increase in the number of MCp's in the lungs. In mice lacking endothelial vascular cell adhesion molecule 1 (VCAM-1) and in wild-type mice administered blocking monoclonal antibody (mAb) to VCAM-1 but not to mucosal addressin CAM-1 (MadCAM-1), recruitment of MCp's to the inflamed lung was reduced by greater than 75%. Analysis of the integrin receptors for VCAM-1 showed that in beta7 integrin-deficient mice, recruitment was reduced 73% relative to wild-type controls, and in either BALB/c or C57BL/6 mice, mAb blocking of alpha4, beta1, or beta7 integrins inhibited the recruitment of MCp's to the inflamed lung. Thus, VCAM-1 interactions with both alpha4beta1 and alpha4beta7 integrins are essential for the recruitment and expansion of the MCp populations in the lung during antigen-induced pulmonary inflammation. Furthermore, the MCp is currently unique among inflammatory cells in its partial dependence on alpha4beta7 integrins for lung recruitment.
正常小鼠肺中缺乏大量肥大细胞（MCs）或MC祖细胞（MCp's），然而气管支气管上皮表面出现成熟MCs是过敏性、T细胞依赖性肺部炎症的一个特征。我们推测肺部炎症会将MCp's招募到炎症肺部，并且这种招募将由不同的黏附途径调节。卵清蛋白致敏和激发的小鼠肺部MCp's数量增加了28倍以上。在内皮血管细胞黏附分子1（VCAM-1）缺失的小鼠以及给予抗VCAM-1而非黏膜地址素细胞黏附分子1（MadCAM-1）阻断单克隆抗体（mAb）的野生型小鼠中，MCp's向炎症肺部的招募减少了75%以上。对VCAM-1的整合素受体分析表明，在β7整合素缺陷小鼠中，相对于野生型对照，招募减少了73%，并且在BALB/c或C57BL/6小鼠中，mAb阻断α4、β1或β7整合素均抑制了MCp's向炎症肺部的招募。因此，在抗原诱导的肺部炎症期间，VCAM-1与α4β1和α4β7整合素的相互作用对于肺部MCp群体的招募和扩增至关重要。此外，MCp目前在炎症细胞中是独特的，因为其肺部招募部分依赖于α4β7整合素。
