Plasminogen is an important regulator in the pathogenesis of a murine model of asthma.
BACKGROUND
Asthma is a syndrome whose common pathogenic expression is inflammation of the airways. Plasminogen plays an important role in cell migration and is also implicated in tissue remodeling, but its role in asthma has not been defined.


OBJECTIVE
To test whether plasminogen is a critical component in the development of asthma.


METHODS
We used a mouse model of ovalbumin-induced pulmonary inflammation in Plg(+/+), Plg(+/-), and Plg(-/-) mice.


RESULTS
The host responses measured included lung morphometry, and inflammatory mediators and cell counts were assessed in bronchoalveolar lavage fluid. Bronchoalveolar lavage demonstrated a marked increase in eosinophils and lymphocytes in ovalbumin-treated Plg(+/+) mice, which were reduced to phosphate-buffered saline-treated control levels in Plg(+/-) or Plg(-/-) mice. Lung histology revealed peribronchial and perivascular leukocytosis, mucus production, and increased collagen deposition in ovalbumin-treated Plg(+/+) but not in Plg(+/-) or Plg(-/-) mice. IL-5, tumor necrosis factor-alpha, and gelatinases, known mediators of asthma, were detected in bronchoalveolar lavage fluid of ovalbumin-treated Plg(+/+) mice, yet were reduced in Plg(-/-) mice. Administration of the plasminogen inhibitor, tranexamic acid, reduced eosinophil and lymphocyte numbers, mucus production, and collagen deposition in the lungs of ovalbumin-treated Plg(+/+) mice.


CONCLUSIONS
The decreased inflammation in the lungs of Plg(-/-) mice and its blockade with a plasminogen inhibitor indicate that plasminogen plays an important role in orchestrating the asthmatic response and suggests that plasminogen may be a therapeutic target for the treatment of asthma.
Swaisgood
Carmen M
CM
Cleveland Clinic, Department of Molecular Cardiology, NB50, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Aronica
Mark A
MA
Swaidani
Shadi
S
Plow
Edward F
EF
D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D018093:Gelatinases / Q000032:analysis; D007249:Inflammation / Q000473:pathology; D015848:Interleukin-5 / Q000032:analysis; D007964:Leukocytosis / Q000473:pathology; D008168:Lung / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D010958:Plasminogen / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D014148:Tranexamic Acid / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000933:Antifibrinolytic Agents; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D014148:Tranexamic Acid; D010958:Plasminogen; D003094:Collagen; D018093:Gelatinases