Neutrophil activation is modulated by sex hormones after trauma-hemorrhagic shock and burn injuries.
Recent literature indicates that females are more resistant to shock-, trauma-, and sepsis-induced immune dysfunction and organ injury than are males. Consequently, using trauma-hemorrhagic shock (T/HS) and burn models, we tested whether the neutrophil response to trauma occurred in a sexually dimorphic fashion and, if so, the role of sex hormones. Neutrophil activation, as reflected by CD11b expression and respiratory burst activity, was increased to a greater extent in male rats than in female rats after T/HS or burn injury. Testosterone appeared to potentiate neutrophil activation, because castration reduced neutrophil activation, whereas ovariectomy had little effect. Mechanistically, this sexually dimorphic neutrophil response appeared to be due to both cellular and humoral factors. Evidence for a cellular difference between male and female neutrophils is based on the observation that naive female neutrophils were more resistant to activation by burn or T/HS plasma and lymph than naive male neutrophils and that this resistance varied over the estrus cycle. Additionally, the humoral environment was more neutrophil activating in male rats, because burn and T/HS plasma and lymph from male rats activated naive male neutrophils to a greater extent than comparable samples from females. Last, on the basis of in vitro experiments examining the effects of estrogen on calcium signaling, it appears that estrogen limits trauma-induced neutrophil activation, at least in part, by limiting the entry of calcium into the cell via store-operated calcium entry mechanisms. In conclusion, there is a striking sexual dimorphism in neutrophil responses after trauma, and these changes reflect both cellular resistance to activation as well as a less activating humoral environment.
Deitch
Edwin A
EA
Department of Surgery, MSB G506, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103, USA. edeitch@umdnj.edu
Ananthakrishnan
Preya
P
Cohen
David B
DB
Xu
Da Zhong
DZ
Feketeova
Eleonora
E
Hauser
Carl J
CJ
D000818:Animals; D002056:Burns / Q000473:pathology / Q000503:physiopathology*; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004054:Diethylstilbestrol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012771:Shock, Hemorrhagic / Q000473:pathology / Q000503:physiopathology*; D013739:Testosterone / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology / Q000503:physiopathology*
D039481:CD11b Antigen; D004967:Estrogens; D013739:Testosterone; D004054:Diethylstilbestrol; D002118:Calcium