Estrogenic hormone modulation abrogates changes in red blood cell deformability and neutrophil activation in trauma hemorrhagic shock.
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.
Doucet
Danielle R
DR
Department of Surgery, New Jersey Medical School, Newark, New Jersey 07103, USA.
Bonitz
R Paul
RP
Feinman
Rena
R
Colorado
Iriana
I
Ramanathan
Mahdury
M
Feketeova
Eleanora
E
Condon
Michael
M
Machiedo
George W
GW
Hauser
Carl J
CJ
Xu
Da-Zhong
DZ
Deitch
Edwin A
EA
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
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