Preprotachykinin-A gene products are key mediators of lung injury in polymicrobial sepsis.
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.
Puneet
Padmam
P
Department of Pharmacology, National University of Singapore, 18 Medical Drive, Singapore 117597.
Hegde
Akhil
A
Ng
Siaw Wei
SW
Lau
Hon Yen
HY
Lu
Jia
J
Moochhala
Shabbir M
SM
Bhatia
Madhav
M
D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D011498:Protein Precursors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D018805:Sepsis / Q000150:complications / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D015996:Survival Rate; D015320:Tachykinins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors
D016207:Cytokines; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin