MMP induced by Gr-1+ cells are crucial for recruitment of Th cells into the airways

Academic Article

Abstract

  • 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 12h 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 24h 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. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
  • Digital Object Identifier (doi)

    Author List

  • Jung YW; Zindl CL; Lai JF; Weaver CT; Chaplin DD
  • Start Page

  • 2281
  • End Page

  • 2292
  • Volume

  • 39
  • Issue

  • 8