title: MMP induced by Gr-1+ cells are crucial for recruitment of Th cells into the airways.
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 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.
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors: Yong Woo
authors: YW
authors: Jung
authors: Carlene L
authors: CL
authors: Zindl
authors: Jen-Feng
authors: JF
authors: Lai
authors: Casey T
authors: CT
authors: Weaver
authors: David D
authors: DD
authors: Chaplin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D015870:Gene Expression; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012137:Respiratory System / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C503133:Gr-1 protein, mouse; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D019715:Tissue Inhibitor of Metalloproteinase-1; D005780:Gelatin; D010047:Ovalbumin; D003094:Collagen; D020782:Matrix Metalloproteinases; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9