title: Proteomic analysis of human mesenteric lymph.
abstract: Extensive animal work has established mesenteric lymph as the mechanistic link between gut ischemia/reperfusion and distant organ injury. Our trauma and transplant services provide a unique opportunity to assess the relevance of our animal data to human mesenteric lymph under conditions that simulate those used in the laboratory. Mesenteric lymph was collected from 11 patients with lymphatic injuries, during semielective spine reconstruction or immediately before organ donation. The lymph was tested for its ability to activate human neutrophils in vitro and was analyzed by label-free proteomic analysis. Human mesenteric lymph primed human polymorphonuclear neutrophils in a pattern similar to that observed in previous rodent, swine, and primate studies. A total of 477 proteins were identified from the 11 subjects' lymph samples with greater than 99% confidence. In addition to classic serum proteins, markers of hemolysis, extracellular matrix components, and general tissue damage were identified. Both tissue injury and shock correlate strongly with production of bioactive lymph. Products of red blood cell hemolysis correlate strongly with human lymph bioactivity, and immunoglobulins have a negative correlation with the proinflammatory lymph. These human data corroborate the current body of research implicating postshock mesenteric lymph in the development of systemic inflammation and multiple organ failure. Further studies will be required to determine if the proteins identified participate in the pathogenesis of multiple organ failure and if they can be used as diagnostic markers.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, Denver, CO, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Dzieciatkowska
authors.forename: Max V
authors.initials: MV
authors.lastname: Wohlauer
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Sagar
authors.initials: S
authors.lastname: Damle
authors.forename: Erik
authors.initials: E
authors.lastname: Peltz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Campsen
authors.forename: Marguerite
authors.initials: M
authors.lastname: Kelher
authors.forename: Christopher
authors.initials: C
authors.lastname: Silliman
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Hansen
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006461:Hemolysis / Q000502:physiology; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008643:Mesentery / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D040901:Proteomics / Q000379:methods*; D013481:Superoxides / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D013481:Superoxides; D000099231:Lipopolysaccharide-Binding Protein