MMP induced by Gr-1+ cells are crucial for recruitment of Th cells into the airways.
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.
Jung
Yong Woo
YW
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Zindl
Carlene L
CL
Lai
Jen-Feng
JF
Weaver
Casey T
CT
Chaplin
David D
DD
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
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