19593770

pubmed:Citation

8

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.

eng

IM

MEDLINE

1521-4141

Electronic

NLM

2281-92

pubmed-meshheading:19593770-Animals, pubmed-meshheading:19593770-Antibodies, Monoclonal, pubmed-meshheading:19593770-Cell Movement, pubmed-meshheading:19593770-Collagen, pubmed-meshheading:19593770-Eosinophils, pubmed-meshheading:19593770-Gelatin, pubmed-meshheading:19593770-Gene Expression, pubmed-meshheading:19593770-Inflammation, pubmed-meshheading:19593770-Lung, pubmed-meshheading:19593770-Matrix Metalloproteinase 8, pubmed-meshheading:19593770-Matrix Metalloproteinase 9, pubmed-meshheading:19593770-Matrix Metalloproteinases, pubmed-meshheading:19593770-Mice, pubmed-meshheading:19593770-Mice, Inbred BALB C, pubmed-meshheading:19593770-Mice, Transgenic, pubmed-meshheading:19593770-Ovalbumin, pubmed-meshheading:19593770-Protease Inhibitors, pubmed-meshheading:19593770-RNA, Messenger, pubmed-meshheading:19593770-Receptors, Chemokine, pubmed-meshheading:19593770-Respiratory System, pubmed-meshheading:19593770-T-Lymphocytes, Helper-Inducer, pubmed-meshheading:19593770-Th1 Cells, pubmed-meshheading:19593770-Th2 Cells, pubmed-meshheading:19593770-Tissue Inhibitor of Metalloproteinase-1

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

Journal Article, Research Support, N.I.H., Extramural