title: 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.affiliation: Department of Pharmacology, National University of Singapore, 18 Medical Drive, Singapore 117597.
authors.forename: Padmam
authors.initials: P
authors.lastname: Puneet
authors.forename: Akhil
authors.initials: A
authors.lastname: Hegde
authors.forename: Siaw Wei
authors.initials: SW
authors.lastname: Ng
authors.forename: Hon Yen
authors.initials: HY
authors.lastname: Lau
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.forename: Shabbir M
authors.initials: SM
authors.lastname: Moochhala
authors.forename: Madhav
authors.initials: M
authors.lastname: Bhatia
mesh_terms: 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
chemical_list: D016207:Cytokines; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin