title: Estrogenic hormone modulation abrogates changes in red blood cell deformability and neutrophil activation in trauma hemorrhagic shock.
abstract: BACKGROUND
  Decreased red blood cell (RBC) deformability and activation of neutrophils (polymorphonuclear leukocytes [PMN]) after trauma-hemorrhagic shock (T/HS) have been implicated in the development of multiple organ dysfunction. Experimentally, female animals seemed to be protected from the effects of T/HS, at least in part, because of elevated estrogen levels. Thus, we examined the relative role of estrogen receptor (ER)-alpha and -beta in this protective response.
  
  
  METHODS
  To accomplish this goal, RBC deformability and neutrophil respiratory burst activity were measured in several groups of hormonally intact or ovariectomized (OVX) female rats subjected to T/HS (laparotomy plus hemorrhage to an MAP of 30 mm Hg to 35 mm Hg for 90 minutes) or trauma-sham shock (T/SS) and 3 hours of reperfusion. These groups included rats receiving vehicle, estradiol, or either an ER-alpha agonist or an ER-beta agonist administered at the end of the shock period just before volume resuscitation.
  
  
  RESULTS
  RBC deformability and neutrophil activation were similar among all the T/SS groups and were not different from that observed in the non-OVX female rats subjected to T/HS. In contrast, RBC deformability was reduced and neutrophil activation was increased in the OVX, T/HS female rats as compared with the T/SS groups or the non-OVX, T/HS rats. The administration of estrogen to the T/HS, OVX rats returned RBC and neutrophil function to normal. Both the ER-alpha and -beta agonist partially, but not completely, protected the OVX rats from T/HS-induced loss of RBC deformability, whereas only the ER-beta agonist prevented the increase in neutrophil activation.
  
  
  CONCLUSIONS
  The protective effects of estrogen on T/HS-induced RBC deformability are mediated, at least in part, via activation of both ER-alpha and -beta, whereas ER-beta activation is involved in limiting T/HS-induced neutrophil activation.
authors.affiliation: Department of Surgery, New Jersey Medical School, Newark, New Jersey 07103, USA.
authors.forename: Danielle R
authors.initials: DR
authors.lastname: Doucet
authors.forename: R Paul
authors.initials: RP
authors.lastname: Bonitz
authors.forename: Rena
authors.initials: R
authors.lastname: Feinman
authors.forename: Iriana
authors.initials: I
authors.lastname: Colorado
authors.forename: Mahdury
authors.initials: M
authors.lastname: Ramanathan
authors.forename: Eleanora
authors.initials: E
authors.lastname: Feketeova
authors.forename: Michael
authors.initials: M
authors.lastname: Condon
authors.forename: George W
authors.initials: GW
authors.lastname: Machiedo
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Hauser
authors.forename: Da-Zhong
authors.initials: DZ
authors.lastname: Xu
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
mesh_terms: D000818:Animals; D004907:Erythrocyte Deformability; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000502:physiology*; D005260:Female; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D010636:Phenols; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000503:physiopathology; D012774:Shock, Traumatic / Q000097:blood* / Q000503:physiopathology
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol