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Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia: a controlled laboratory study.

Schouten M, van't Veer C, Roelofs JJ, Levi M, van der Poll T - Crit Care (2012)

Bottom Line: The cellular effect of PAR-1 activation partially depends on the specific protease involved.We here determined the role of PAR-1 in the host response during murine pneumococcal pneumonia.PAR-1 impairs host defense during murine pneumococcal pneumonia.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. Protease-activated receptor-1 (PAR-1) is expressed by multiple cell types present in the lungs and can be activated by various proteases generated during acute inflammation. The cellular effect of PAR-1 activation partially depends on the specific protease involved. We here determined the role of PAR-1 in the host response during murine pneumococcal pneumonia.

Methods: Wild-type (WT) and PAR-1 knockout (KO) mice were infected intranasally with viable S. pneumoniae and observed in a survival study or euthanized at 6, 24 or 48 hours of infection.

Results: PAR-1 KO mice had a better survival early after infection compared to WT mice. Moreover, PAR-1 KO mice had lower bacterial loads in lungs and blood at 24 hours and in spleen and liver at 48 hours after infection. This favorable response was accompanied by lower lung histopathology scores and less neutrophil influx in PAR-1 KO mice.

Conclusion: PAR-1 impairs host defense during murine pneumococcal pneumonia.

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Related in: MedlinePlus

Reduced pulmonary neutrophil influx in protease-activated receptor-1 knockout mice in later stage of murine pneumococcal pneumonia. Representative slides of lung Ly-6G staining (brown) 24 and 48 hours after induction of pneumococcal pneumonia in (A) wild-type and (B) protease-activated receptor-1 knockout mice (200 times original magnification). (C) Quantitation of pulmonary Ly-6G 48 hours after induction of pneumococcal pneumonia in wild-type (open bars) and protease-activated receptor-1 knockout mice (grey bars). Data are expressed as box-and-whisker diagrams depicting the smallest observation, lower quartile, median, upper quartile and largest observation (eight mice per group). * indicates statistical significance as compared to wild-type (P <0.05, Mann-Whitney U test).
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Figure 4: Reduced pulmonary neutrophil influx in protease-activated receptor-1 knockout mice in later stage of murine pneumococcal pneumonia. Representative slides of lung Ly-6G staining (brown) 24 and 48 hours after induction of pneumococcal pneumonia in (A) wild-type and (B) protease-activated receptor-1 knockout mice (200 times original magnification). (C) Quantitation of pulmonary Ly-6G 48 hours after induction of pneumococcal pneumonia in wild-type (open bars) and protease-activated receptor-1 knockout mice (grey bars). Data are expressed as box-and-whisker diagrams depicting the smallest observation, lower quartile, median, upper quartile and largest observation (eight mice per group). * indicates statistical significance as compared to wild-type (P <0.05, Mann-Whitney U test).

Mentions: To investigate the impact of PAR-1 on lung pathology, we determined histopathology scores of lung tissue slides obtained 24 and 48 hours after infection. Pneumococcal pneumonia was associated with pulmonary inflammation and damage as evidenced by the occurrence of bronchitis, interstitial inflammation, edema and endothelialitis. Mean histopathological scores were lower in PAR-1 KO mice at both 24 and 48 hours after infection (Figure 3A to 3C). To obtain insight in the role of PAR-1 in neutrophil recruitment to the primary site of infection, we performed Ly-6G staining on lung sections at 24 and 48 hours after infection. While there were no significant differences at 24 hours after infection, PAR-1 KO mice showed significantly lower neutrophil numbers in lung tissue later on, as evidenced by lower Ly-6G positivity at 48 hours after infection (Figure 4A to 4C).


Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia: a controlled laboratory study.

Schouten M, van't Veer C, Roelofs JJ, Levi M, van der Poll T - Crit Care (2012)

Reduced pulmonary neutrophil influx in protease-activated receptor-1 knockout mice in later stage of murine pneumococcal pneumonia. Representative slides of lung Ly-6G staining (brown) 24 and 48 hours after induction of pneumococcal pneumonia in (A) wild-type and (B) protease-activated receptor-1 knockout mice (200 times original magnification). (C) Quantitation of pulmonary Ly-6G 48 hours after induction of pneumococcal pneumonia in wild-type (open bars) and protease-activated receptor-1 knockout mice (grey bars). Data are expressed as box-and-whisker diagrams depicting the smallest observation, lower quartile, median, upper quartile and largest observation (eight mice per group). * indicates statistical significance as compared to wild-type (P <0.05, Mann-Whitney U test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672627&req=5

Figure 4: Reduced pulmonary neutrophil influx in protease-activated receptor-1 knockout mice in later stage of murine pneumococcal pneumonia. Representative slides of lung Ly-6G staining (brown) 24 and 48 hours after induction of pneumococcal pneumonia in (A) wild-type and (B) protease-activated receptor-1 knockout mice (200 times original magnification). (C) Quantitation of pulmonary Ly-6G 48 hours after induction of pneumococcal pneumonia in wild-type (open bars) and protease-activated receptor-1 knockout mice (grey bars). Data are expressed as box-and-whisker diagrams depicting the smallest observation, lower quartile, median, upper quartile and largest observation (eight mice per group). * indicates statistical significance as compared to wild-type (P <0.05, Mann-Whitney U test).
Mentions: To investigate the impact of PAR-1 on lung pathology, we determined histopathology scores of lung tissue slides obtained 24 and 48 hours after infection. Pneumococcal pneumonia was associated with pulmonary inflammation and damage as evidenced by the occurrence of bronchitis, interstitial inflammation, edema and endothelialitis. Mean histopathological scores were lower in PAR-1 KO mice at both 24 and 48 hours after infection (Figure 3A to 3C). To obtain insight in the role of PAR-1 in neutrophil recruitment to the primary site of infection, we performed Ly-6G staining on lung sections at 24 and 48 hours after infection. While there were no significant differences at 24 hours after infection, PAR-1 KO mice showed significantly lower neutrophil numbers in lung tissue later on, as evidenced by lower Ly-6G positivity at 48 hours after infection (Figure 4A to 4C).

Bottom Line: The cellular effect of PAR-1 activation partially depends on the specific protease involved.We here determined the role of PAR-1 in the host response during murine pneumococcal pneumonia.PAR-1 impairs host defense during murine pneumococcal pneumonia.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. Protease-activated receptor-1 (PAR-1) is expressed by multiple cell types present in the lungs and can be activated by various proteases generated during acute inflammation. The cellular effect of PAR-1 activation partially depends on the specific protease involved. We here determined the role of PAR-1 in the host response during murine pneumococcal pneumonia.

Methods: Wild-type (WT) and PAR-1 knockout (KO) mice were infected intranasally with viable S. pneumoniae and observed in a survival study or euthanized at 6, 24 or 48 hours of infection.

Results: PAR-1 KO mice had a better survival early after infection compared to WT mice. Moreover, PAR-1 KO mice had lower bacterial loads in lungs and blood at 24 hours and in spleen and liver at 48 hours after infection. This favorable response was accompanied by lower lung histopathology scores and less neutrophil influx in PAR-1 KO mice.

Conclusion: PAR-1 impairs host defense during murine pneumococcal pneumonia.

Show MeSH
Related in: MedlinePlus