Preprotachykinin-A Gene Products Are Key Mediators of Lung Injury in Polymicrobial Sepsis

• Published in: Journal of Immunology 2006-03, Vol.176 (6), p.3813-3820
• Main Authors: Puneet, Padmam, Hegde, Akhil, Ng, Siaw Wei, Lau, Hon Yen, Lu, Jia, Moochhala, Shabbir M, Bhatia, Madhav
• Format: Article
• Language: English
• Subjects: Animals; Cell Proliferation; Cytokines - biosynthesis; Gene Deletion; Male; Mice; Mice, Knockout; Neutrophils - cytology; Neutrophils - metabolism; Protein Precursors - deficiency; Protein Precursors - genetics; Protein Precursors - metabolism; Respiratory Distress Syndrome, Adult - complications; Respiratory Distress Syndrome, Adult - metabolism; Respiratory Distress Syndrome, Adult - microbiology; Respiratory Distress Syndrome, Adult - pathology; Sepsis - complications; Sepsis - metabolism; Sepsis - microbiology; Sepsis - pathology; Survival Rate; Tachykinins - deficiency; Tachykinins - genetics; Tachykinins - metabolism; Time Factors
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.176.6.3813

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.