title: Trauma-hemorrhagic shock induces a CD36-dependent RBC endothelial-adhesive phenotype.
abstract: OBJECTIVE
  Microvascular dysfunction is a key element in the development of the multiple organ dysfunction syndrome. Although the mechanisms for this response are unclear, RBC adhesion to endothelium may initiate intravascular occlusion leading to ischemic tissue injury. Thus, we tested the hypothesis that trauma-hemorrhage induces RBC-endothelial cell adhesion.
  
  
  METHODS
  Prospective in vivo and in vitro animal study and analysis of patient blood samples.
  
  
  METHODS
  University research laboratory and hospital emergency and trauma units.
  
  
  METHODS
  We initially assayed RBC adhesion to endothelial cells in vitro using RBCs obtained from rats subjected to trauma-hemorrhagic shock or sham shock as well as from severely injured trauma patients. Subsequently, we measured the role of putative RBCs and endothelial cell receptors in the increased RBC-endothelial cell adhesive response.
  
  
  RESULTS
  In both rats and humans, trauma-hemorrhagic shock increased RBC adhesion to endothelium as well as increasing several putative RBC surface adhesion molecules including CD36. The critical factor leading to RBC-endothelial cell adhesion was increased surface RBC CD36 expression. Adhesion of trauma-hemorrhagic shock RBCs was mediated, at least in part, by the binding of RBC CD36 to its cognate endothelial receptors (αVβ3 and VCAM-1). Gut-derived factors carried in the intestinal lymphatics triggered these trauma-hemorrhagic shock-induced RBC changes because 1) preventing trauma-hemorrhagic shock intestinal lymph from reaching the systemic circulation abrogated the RBC effects, 2) in vitro incubation of naïve whole blood with trauma-hemorrhagic shock lymph replicated the in vivo trauma-hemorrhagic shock-induced RBC changes while 3) injection of trauma-hemorrhagic shock lymph into naïve animals recreated the RBC changes observed after actual trauma-hemorrhagic shock.
  
  
  CONCLUSIONS
  1) Trauma-hemorrhagic shock induces rapid RBC adhesion to endothelial cells in patients and animals. 2) Increased RBC CD36 expression characterizes the RBC-adhesive phenotype. 3) The RBC phenotypic and functional changes were induced by gut-derived humoral factors. These novel findings may explain the microvascular dysfunction occurring after trauma-hemorrhagic shock, sepsis, and other stress states.
authors: 1Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ. 2Surgical Services, VA New Jersey Healthcare System, East Orange, NJ. 3Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ.
authors: Edwin A
authors: EA
authors: Deitch
authors: Michael
authors: M
authors: Condon
authors: Eleonora
authors: E
authors: Feketeova
authors: George W
authors: GW
authors: Machiedo
authors: Leonard
authors: L
authors: Mason
authors: Ghia M
authors: GM
authors: Vinluan
authors: Vamsi A
authors: VA
authors: Alli
authors: Matthew D
authors: MD
authors: Neal
authors: Jacquelyn N
authors: JN
authors: Tomaio
authors: Jordan E
authors: JE
authors: Fishman
authors: Walter N
authors: WN
authors: Durán
authors: Zoltan
authors: Z
authors: Spolarics
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D004912:Erythrocytes / Q000166:cytology* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009102:Multiple Organ Failure / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012774:Shock, Traumatic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D018955:CD36 Antigens