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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

Lower bacterial outgrowth in protease-activated receptor-1 knockout mice in lungs and blood at 24 hours and in spleen and liver at 48 hours after induction of murine pneumococcal pneumonia. Bacterial outgrowth in (A) lung, (B) blood, (C) spleen and (D) liver 6, 24, and 48 hours after induction of pneumococcal pneumonia in wild-type (open bars) and protease-activated receptor-1 knockout (grey bars) mice. 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 2: Lower bacterial outgrowth in protease-activated receptor-1 knockout mice in lungs and blood at 24 hours and in spleen and liver at 48 hours after induction of murine pneumococcal pneumonia. Bacterial outgrowth in (A) lung, (B) blood, (C) spleen and (D) liver 6, 24, and 48 hours after induction of pneumococcal pneumonia in wild-type (open bars) and protease-activated receptor-1 knockout (grey bars) mice. 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 determine whether the difference in survival between PAR-1 KO and WT mice in pneumococcal pneumonia could be attributed to a difference in antibacterial defense, we determined bacterial outgrowth 6, 24 and 48 hours in lungs, blood and distant organs (spleen, liver) (Figure 2). At 6 hours after infection, there were no differences in pulmonary bacterial loads between PAR-1 KO and WT mice (Figure 2A). At this time point, bacteria could not be detected in blood and distant organs (Figure 2B to 2D). At 24 hours, PAR-1 KO mice had markedly lower bacterial burdens in their lungs (Figure 2A) and blood (Figure 2B) with a trend toward lower levels in spleen (P = 0.18) (Figure 2C) as compared to WT mice. Whereas at 48 hours the differences in bacterial outgrowth in lung and blood had subsided (Figure 2A to 2B), PAR-1 KO mice had lower bacterial loads in spleen (Figure 2C) and liver (Figure 2D) as compared to WT mice.


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)

Lower bacterial outgrowth in protease-activated receptor-1 knockout mice in lungs and blood at 24 hours and in spleen and liver at 48 hours after induction of murine pneumococcal pneumonia. Bacterial outgrowth in (A) lung, (B) blood, (C) spleen and (D) liver 6, 24, and 48 hours after induction of pneumococcal pneumonia in wild-type (open bars) and protease-activated receptor-1 knockout (grey bars) mice. 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 2: Lower bacterial outgrowth in protease-activated receptor-1 knockout mice in lungs and blood at 24 hours and in spleen and liver at 48 hours after induction of murine pneumococcal pneumonia. Bacterial outgrowth in (A) lung, (B) blood, (C) spleen and (D) liver 6, 24, and 48 hours after induction of pneumococcal pneumonia in wild-type (open bars) and protease-activated receptor-1 knockout (grey bars) mice. 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 determine whether the difference in survival between PAR-1 KO and WT mice in pneumococcal pneumonia could be attributed to a difference in antibacterial defense, we determined bacterial outgrowth 6, 24 and 48 hours in lungs, blood and distant organs (spleen, liver) (Figure 2). At 6 hours after infection, there were no differences in pulmonary bacterial loads between PAR-1 KO and WT mice (Figure 2A). At this time point, bacteria could not be detected in blood and distant organs (Figure 2B to 2D). At 24 hours, PAR-1 KO mice had markedly lower bacterial burdens in their lungs (Figure 2A) and blood (Figure 2B) with a trend toward lower levels in spleen (P = 0.18) (Figure 2C) as compared to WT mice. Whereas at 48 hours the differences in bacterial outgrowth in lung and blood had subsided (Figure 2A to 2B), PAR-1 KO mice had lower bacterial loads in spleen (Figure 2C) and liver (Figure 2D) as compared to WT mice.

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