Jung Yong Woo, Zindl Carlene L, Lai Jen-Feng, Weaver Casey T, Chaplin David D
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Eur J Immunol. 2009 Aug;39(8):2281-92. doi: 10.1002/eji.200838985.
Th2 lymphocytes deliver essential signals for induction of asthmatic airway inflammation. We previously found that airway antigen challenge induces recruitment of Gr-1(+) neutrophils prior to the recruitment of Th2 cells. We examined, therefore, whether Gr-1(+) cells contribute to the development of Th2-dependent airway inflammation. Systemic depletion of Gr-1(+) cells using the RB6-8C5 monoclonal antibody reduced Th2 cell recruitment following i.n. antigen challenge. The levels of both MMP-9 and the tissue inhibitor of matrix metalloproteinases-1 mRNA were up-regulated in the lungs of mice 12 h after i.n. antigen challenge. Up-regulation of tissue inhibitor of matrix metalloproteinases-1 was independent of Gr-1(+) cells, whereas up-regulation of MMP-9 RNA and total gelatinolytic activity was dramatically reduced in mice depleted of Gr-1(+) cells. At 24 h after challenge, total lung collagenolytic activity was also up-regulated, in a Gr-1(+) cell-dependent fashion. Systemic inhibition of MMP-8 and MMP-9 reduced the airway recruitment of Th cells, resulting in significantly reduced eosinophilic inflammation. These data suggest that antigen challenge via the airway activates Gr-1(+) cells and consequently MMP to facilitate the recruitment of Th cells in the airway inflammatory response.
Th2淋巴细胞为哮喘气道炎症的诱导传递关键信号。我们先前发现气道抗原激发在Th2细胞募集之前会诱导Gr-1(+)中性粒细胞的募集。因此，我们研究了Gr-1(+)细胞是否有助于Th2依赖性气道炎症的发展。使用RB6-8C5单克隆抗体对Gr-1(+)细胞进行全身清除，可减少经鼻内抗原激发后的Th2细胞募集。鼻内抗原激发12小时后，小鼠肺中基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶组织抑制剂-1（TIMP-1）mRNA的水平均上调。TIMP-1的上调与Gr-1(+)细胞无关，而在Gr-1(+)细胞清除的小鼠中，MMP-9 RNA的上调和总明胶酶活性显著降低。激发后24小时，全肺胶原酶活性也以Gr-1(+)细胞依赖的方式上调。对MMP-8和MMP-9的全身抑制减少了Th细胞的气道募集，导致嗜酸性炎症显著减轻。这些数据表明，通过气道的抗原激发激活了Gr-1(+)细胞，进而激活基质金属蛋白酶，以促进气道炎症反应中Th细胞的募集。
