Table 1.
Summary of experiments indicating the role of plasminogen activator system in animal models of disease
AuthorsModelPlasmin(ogen) roletPA roleuPA roleFibrin dependent?
Infection 
Nordstrand et al., 2001  Plg−/− mice on C57Bl/6 background Aids in infection by B. crocidurae    
Gebbia et al., 1999  Plg−/− mice on mixed 129/Black Swiss background Increases bacterial load in inflammation in brains and hearts of mice treated with B. burgdorferi    
Coleman et al., 1995  Human umbilical vein endothelial cells Aids in B. burgdorferi penetration of endothelium    
Guo et al., 2011  Plg−/−, tPA−/−, and uPA−/− mice on C57Bl/6 background Aids in infection by S. aureus Aids in infection by S. aureus Aids in infection by S. aureus  
Berri et al., 2013  Plg−/− mice on C57Bl/6 background Aids in lung inflammation in response to infection with H5N1 and H1N1 viruses   Yes 
Stie and Fox, 2012a, 2012b  Primary cultured BMEC Used by the fungus C. neoformans to invade its host  Upregulated in response to C. neoformans infection  
González-Miguel et al., 2019  Wistar rats Enhanced generation in response to parasite F. hepatica infection    
Silva et al., 2019  Plg−/− and Fbg−/− mice on C57Bl/6 background Necessary for macrophage migration in sterile peritonitis   Yes 
Neurological disease 
Tsirka et al., 1997a, 1997b  C57Bl/6 mice Regulates neuronal death in response to acute kainate injection Regulates microglial activation and neuronal death in response to acute kainate injection  No 
Hultman et al., 2014  Plg−/− mice on a C57Bl/6 background Promotes neuroinflammation in response to acute LPS challenge   No 
Baker et al., 2019  C57Bl/6 mice Recruits perivascular macrophage migration and microglial activation in response to peripheral LPS challenge    
Paul et al., 2007  Plg−/− AD mice Contributes to neurovascular damage in a mouse model of AD   Yes 
Shaw et al., 2017  Plg−/− mice on a C57Bl/6 background Promotes demyelination in EAE model   Yes 
Baker et al., 2018  Tg6799 mice Promotes neuroinflammation and AD pathology    
Siao and Tsirka, 2002  tPA−/− mice on a C57Bl/6 background  Promotes microglial activation in response to LPS   
East et al., 2005; Dahl et al., 2016  tPA−/− mice on a C57Bl/6 background  Protects against early onset and severe demyelination in EAE model  Yes 
Lenglet et al., 2014  129/SvEV mice  Increases inflammation following stroke  No 
Arthritis 
Li et al., 2005  uPA−/− and Plg−/− mice on a C57Bl/6 background Promotes joint inflammation in systemic collagen type II–induced arthritis  Promotes joint inflammation in collagen type II–induced arthritis  
Raghu et al., 2014  Plg−/− mice on a C57Bl/6 background Prevents joint inflammation in small joints and promotes inflammation in large joints in a monoarticular TNF-α arthritis model   Yes 
Cook et al., 2010  uPA−/− mice on a C57Bl/6 background   Necessary for systemic arthritis development  
De Nardo et al., 2010  uPA−/− mice on a C57Bl/6 background   Limits susceptibility to monoarticular arthritis Yes 
Other 
Das et al., 2013  Plg−/− mice on a C57Bl/6 background Promotes atherosclerosis progression via regulation of foam cell formation    
DeFilippis et al., 2016  Humans with myocardial infarction Binds to OxPLs to regulate inflammation in myocardial infarction events   Yes 
Swaisgood et al., 2007  Plg−/− mice on a C57Bl/6 background Promotes mucus production and immune cell recruitment into lungs of ovalbumin-induced asthma model    
Li et al., 2011  BALB/c mice Plasminogen is decreased and plasmin is increased in psoriatic lesions, promoting upregulation of chemokines    
AuthorsModelPlasmin(ogen) roletPA roleuPA roleFibrin dependent?
Infection 
Nordstrand et al., 2001  Plg−/− mice on C57Bl/6 background Aids in infection by B. crocidurae    
Gebbia et al., 1999  Plg−/− mice on mixed 129/Black Swiss background Increases bacterial load in inflammation in brains and hearts of mice treated with B. burgdorferi    
Coleman et al., 1995  Human umbilical vein endothelial cells Aids in B. burgdorferi penetration of endothelium    
Guo et al., 2011  Plg−/−, tPA−/−, and uPA−/− mice on C57Bl/6 background Aids in infection by S. aureus Aids in infection by S. aureus Aids in infection by S. aureus  
Berri et al., 2013  Plg−/− mice on C57Bl/6 background Aids in lung inflammation in response to infection with H5N1 and H1N1 viruses   Yes 
Stie and Fox, 2012a, 2012b  Primary cultured BMEC Used by the fungus C. neoformans to invade its host  Upregulated in response to C. neoformans infection  
González-Miguel et al., 2019  Wistar rats Enhanced generation in response to parasite F. hepatica infection    
Silva et al., 2019  Plg−/− and Fbg−/− mice on C57Bl/6 background Necessary for macrophage migration in sterile peritonitis   Yes 
Neurological disease 
Tsirka et al., 1997a, 1997b  C57Bl/6 mice Regulates neuronal death in response to acute kainate injection Regulates microglial activation and neuronal death in response to acute kainate injection  No 
Hultman et al., 2014  Plg−/− mice on a C57Bl/6 background Promotes neuroinflammation in response to acute LPS challenge   No 
Baker et al., 2019  C57Bl/6 mice Recruits perivascular macrophage migration and microglial activation in response to peripheral LPS challenge    
Paul et al., 2007  Plg−/− AD mice Contributes to neurovascular damage in a mouse model of AD   Yes 
Shaw et al., 2017  Plg−/− mice on a C57Bl/6 background Promotes demyelination in EAE model   Yes 
Baker et al., 2018  Tg6799 mice Promotes neuroinflammation and AD pathology    
Siao and Tsirka, 2002  tPA−/− mice on a C57Bl/6 background  Promotes microglial activation in response to LPS   
East et al., 2005; Dahl et al., 2016  tPA−/− mice on a C57Bl/6 background  Protects against early onset and severe demyelination in EAE model  Yes 
Lenglet et al., 2014  129/SvEV mice  Increases inflammation following stroke  No 
Arthritis 
Li et al., 2005  uPA−/− and Plg−/− mice on a C57Bl/6 background Promotes joint inflammation in systemic collagen type II–induced arthritis  Promotes joint inflammation in collagen type II–induced arthritis  
Raghu et al., 2014  Plg−/− mice on a C57Bl/6 background Prevents joint inflammation in small joints and promotes inflammation in large joints in a monoarticular TNF-α arthritis model   Yes 
Cook et al., 2010  uPA−/− mice on a C57Bl/6 background   Necessary for systemic arthritis development  
De Nardo et al., 2010  uPA−/− mice on a C57Bl/6 background   Limits susceptibility to monoarticular arthritis Yes 
Other 
Das et al., 2013  Plg−/− mice on a C57Bl/6 background Promotes atherosclerosis progression via regulation of foam cell formation    
DeFilippis et al., 2016  Humans with myocardial infarction Binds to OxPLs to regulate inflammation in myocardial infarction events   Yes 
Swaisgood et al., 2007  Plg−/− mice on a C57Bl/6 background Promotes mucus production and immune cell recruitment into lungs of ovalbumin-induced asthma model    
Li et al., 2011  BALB/c mice Plasminogen is decreased and plasmin is increased in psoriatic lesions, promoting upregulation of chemokines    

Note that fibrinogen dependence is indicated only if it was specifically studied in the particular experiment described. BMEC, brain microvascular endothelial cells.

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