title: Patterns of gene expression among murine models of hemorrhagic shock/trauma and sepsis.
abstract: Controversy remains whether the leukocyte genomic response to trauma or sepsis is dependent upon the initiating stimulus. Previous work illustrated poor correlations between historical models of murine trauma and sepsis (i.e., trauma-hemorrhage and lipopolysaccharide injection, respectively). The aim of this study is to examine the early genomic response in improved murine models of sepsis [cecal ligation and puncture (CLP)] and trauma [polytrauma (PT)] with and without pneumonia (PT+Pp). Groups of naïve, CLP, PT, and PT+Pp mice were killed at 2 h, 1 or 3 days. Total leukocytes were isolated for genome-wide expression analysis, and genes that were found to differ from control (false discovery rate adjusted P < 0.001) were assessed for fold-change differences. Spearman correlations were also performed. For all time points combined (CLP, PT, PT+Pp), there were 10,426 total genes that were found to significantly differ from naïve controls. At 2 h, the transcriptomic changes between CLP and PT showed a positive correlation (rs) of 0.446 (P < 0.0001) but were less positive thereafter. Correlations were significantly improved when we limited the analysis to common genes whose expression differed by a 1.5 fold-change. Both pathway and upstream analyses revealed the activation of genes known to be associated with pathogen-associated and damage-associated molecular pattern signaling, and early activation patterns of expression were very similar between polytrauma and sepsis at the earliest time points. This study demonstrates that the early leukocyte genomic response to sepsis and trauma are very similar in mice.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Mira
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Szpila
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Maria-Cecilia
authors.initials: MC
authors.lastname: Lopez
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Lori F
authors.initials: LF
authors.lastname: Gentile
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Brittany J
authors.initials: BJ
authors.lastname: Mathias
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Vanzant
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ungaro
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: David
authors.initials: D
authors.lastname: Holden
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Rosenthal
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Jaimar
authors.initials: J
authors.lastname: Rincon
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Verdugo
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Larson
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Moore
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Brakenridge
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Mohr
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Henry V
authors.initials: HV
authors.lastname: Baker
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida; and philip.efron@surgery.ufl.edu.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005189:False Positive Reactions; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D007107:Immune System; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology; D008214:Lymphocytes / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009104:Multiple Trauma / Q000378:metabolism* / Q000503:physiopathology; D011014:Pneumonia / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction
keywords: cecal ligation and puncture; correlations; mouse; polytrauma; transcriptomics