title: Normal mesenteric lymph blunts the pulmonary inflammatory response to endotoxin.
abstract: BACKGROUND
  Mesenteric lymph may provide the mechanistic link between gut ischemia and acute lung injury after hemorrhagic shock (HS). Studies have focused on the toxic mediators that develop in the post-shock mesenteric lymph (PSML). However, a complementary possibility is that there is loss of protective mediators found in pre-shock normal mesenteric lymph (NML) after HS. We hypothesize that NML protects against inflammatory insults to the pulmonary endothelium and that this effect is lost in PSML.
  
  
  METHODS
  Primary human pulmonary endothelial cells (HMVECs) were incubated with NML or PSML collected from rats subjected to HS and resuscitation and then stimulated with 20 ng/mL LPS. ICAM-1 surface expression was measured by flow cytometry. In subsequent experiments, lipoproteins were extracted from NML before incubation and LPS-induced ICAM-1 expression determined.
  
  
  RESULTS
  Mean fluorescent intensity (MFI) of LPS-induced ICAM-1 in NML and PSML treated HMVECs were 10.1 +/- 2.3 versus 27.7 +/- 0.83, respectively (P < 0.05). This represented at 71% decrease in ICAM-1 expression by NML compared to ICAM-1 expression in LPS-induced controls (MFI: 34.6 +/- 6.9). Lipoprotein extraction from NML abolished this protective effect (MFI: 31.2 +/- 5.3 versus Control + LPS: 33.5 +/- 3.6, P > 0.05). Baseline ICAM-1 levels were not significantly different among control, NML, and PSML groups.
  
  
  CONCLUSIONS
  Lipoproteins in NML contain anti-inflammatory properties that decrease ICAM-1 expression induced by LPS in pulmonary endothelium. Decreased protective lipoproteins after HS and resuscitation may contribute to the toxicity associated with PSML from the ischemic gut.
authors.affiliation: Department of Surgery, Denver Health Medical Center, University of Colorado Health Sciences Center, Denver, Colorado 80204, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Cheng
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Masuno
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Escobar
authors.forename: Eric L
authors.initials: EL
authors.lastname: Sarin
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Phillip
authors.initials: P
authors.lastname: Eckels
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D019446:Endotoxemia / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007511:Ischemia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000378:metabolism; D008208:Lymphatic System / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008643:Mesentery; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000418:Albumins; D008070:Lipopolysaccharides; D008074:Lipoproteins; D014280:Triglycerides; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol