Preprotachykinin-A gene products are key mediators of lung injury in polymicrobial sepsis.

Abstract

Preprotachykinin-A (PPT-A) gene products substance P and neurokinin-A have been shown to play an important role in neurogenic inflammation. To investigate the role of PPT-A gene products in lung injury in sepsis, polymicrobial sepsis was induced by cecal ligation and puncture in PPT-A gene-deficient mice (PPT-A(-/-)) and the wild-type control mice (PPT-A(+/+)). PPT-A gene deletion significantly protected against mortality, delayed the onset of lethality, and improved the long-term survival following cecal ligation and puncture-induced sepsis. PPT-A(-/-) mice also had significantly attenuated inflammation and damage in the lungs. The data suggest that deletion of the PPT-A gene may have contributed to the disruption in recruitment of inflammatory cells resulting in protection against tissue damage, as in these mice the sepsis-associated increase in chemokine levels is significantly attenuated.

• Authors: Padmam Puneet, Akhil Hegde, Siaw Wei Ng, Hon Yen Lau, Jia Lu, Shabbir M Moochhala, Madhav Bhatia
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 6 Pg. 3813-20 (Mar 15 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16517752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Protein Precursors
• Tachykinins
• preprotachykinin

Topics

• Animals
• Cell Proliferation
• Cytokines (biosynthesis)
• Gene Deletion
• Male
• Mice
• Mice, Knockout
• Neutrophils (cytology, metabolism)
• Protein Precursors (deficiency, genetics, metabolism)
• Respiratory Distress Syndrome (complications, metabolism, microbiology, pathology)
• Sepsis (complications, metabolism, microbiology, pathology)
• Survival Rate
• Tachykinins (deficiency, genetics, metabolism)
• Time Factors