Testosterone Depletion or Blockade in Male Rats Protects Against Trauma Hemorrhagic Shock-Induced Distant Organ Injury by Limiting Gut Injury and Subsequent Production of Biologically Active Mesenteric Lymph

CD103+ dendritic cells (DCs) continuously migrate from the intestine to the mesenteric lymph nodes (MLNs) and maintain tolerance by driving the development of regulatory T cells (Treg) in the gut. The relative expression of Treg and T-helper 17 (Th17) cells determines the balance between tolerance and immunity in the gut. We hypothesized that trauma/hemorrhagic shock (T/HS) would decrease the CD103+ DC population in the mesenteric lymph and alter the Treg-to-Th17 ratio in the MLN. We further hypothesized that vagus nerve stimulation (VNS) would promote tolerance to inflammation by increasing the Treg-to-Th17 ratio in the MLN after injury. Male rats were assigned to sham shock (SS), trauma/sham shock (T/SS), or T/HS. T/HS was induced by laparotomy and 60 min of HS (blood pressure 35 mmHg) followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. MLN samples were collected 24 h after resuscitation. The CD103+ DC population and Treg-to-Th17 cell ratio in the MLN were decreased after T/HS compared with SS and T/SS, suggesting a shift to an inflammatory response. VNS prevented the T/HS-induced decrease in the CD103+ DC population and increased the Treg-to-Th17 ratio compared with T/HS alone. VNS alters the gut inflammatory response to injury by modulating the Treg-Th17 cell balance in the MLN. VNS promotes tolerance to inflammation in the gut, further supporting its ability to modulate the inflammatory set point and alter the response to injury.

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Sex Hormones Modulate Distant Organ Injury in Both a Trauma/Hemorrhagic Shock Model and a Burn Model

Yearbook of Surgery ◽

10.1016/s0090-3671(08)70344-6 ◽

2006 ◽

Vol 2006 ◽

pp. 58

Author(s):

D.W. Mozingo

Keyword(s):

Hemorrhagic Shock ◽

Sex Hormones ◽

Organ Injury ◽

Shock Model ◽

Distant Organ ◽

Hemorrhagic Shock Model

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MESENTERIC LYMPH IS THE LINK BETWEEN THE GUT AND DISTANT ORGAN INJURY

Shock ◽

10.1097/00024382-199911001-00073 ◽

1999 ◽

Vol 12 (Supplement) ◽

pp. 24

Author(s):

E. A. Deitch

Keyword(s):

Organ Injury ◽

Mesenteric Lymph ◽

Distant Organ

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Neutrophil activation is modulated by sex hormones after trauma-hemorrhagic shock and burn injuries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00694.2005 ◽

2006 ◽

Vol 291 (3) ◽

pp. H1456-H1465 ◽

Cited By ~ 51

Author(s):

Edwin A. Deitch ◽

Preya Ananthakrishnan ◽

David B. Cohen ◽

Da Zhong Xu ◽

Eleonora Feketeova ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Sex Hormones ◽

Burn Injury ◽

Neutrophil Activation ◽

Female Rats ◽

Organ Injury ◽

Male Rats ◽

Sexually Dimorphic ◽

Humoral Factors ◽

Neutrophil Response

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.

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Intravenous injection of post‑hemorrhagic shock mesenteric lymph induces multiple organ injury in rats

Experimental and Therapeutic Medicine ◽

10.3892/etm.2018.7048 ◽

2018 ◽

Cited By ~ 1

Author(s):

Yifeng Zhao ◽

Limin Zhang ◽

Rui Han ◽

Yonghua Si ◽

Zigang Zhao

Keyword(s):

Hemorrhagic Shock ◽

Intravenous Injection ◽

Multiple Organ ◽

Organ Injury ◽

Mesenteric Lymph ◽

Multiple Organ Injury

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RAS Equilibrium Involves in Mesenteric Lymph Return-Mediated Acute Kidney Injury in Mice Underwent Acute Hemorrhage

10.21203/rs.3.rs-38715/v1 ◽

2020 ◽

Author(s):

Yu-Jie Jin ◽

Kun Su ◽

Hong Zhang ◽

Jin Xie ◽

Hong Sun ◽

...

Keyword(s):

Acute Kidney Injury ◽

Hemorrhagic Shock ◽

Tissue Injury ◽

Kidney Injury ◽

Organ Injury ◽

Ang Ii ◽

Acute Hemorrhage ◽

Mesenteric Lymph ◽

Duct Ligation

Abstract Background: Previous studies demonstrated renin-angiotensin system (RAS) played vital roles in shock-induced organ injury, and mesenteric lymph return was involved in hemorrhagic shock-induced acute kidney injury (AKI). Nevertheless, whether RAS is involved in PHSML-mediated AKI remains unclear. Therefore, this study investigated the role of RAS in post-hemorrhagic shock mesenteric lymph (PHSML)-induced AKI. Methods: After acute hemorrhage and fluid resuscitation, the mice were treated with mesenteric lymph duct ligation (MLDL) and administrations of angiotensin converting enzyme (ACE) inhibitor enalapril, angiotensin (1-7) (Ang (1-7)), angiotensin II (Ang II) type 1 receptor (AT1R) inhibitor losartan, respectively. In addition, the parts of mice with hemorrhage plus MLDL were treated with Ang II, Mas receptor (MasR) inhibitor A-779, respectively. Meanwhile, the ACE2-/- mice received hemorrhage plus MLDL. At 4 h after resuscitation, the kidneys were harvested for the observation of histomorphology and measurement of ACE, ACE2, AT1R, MasR expressions and Ang II and Ang (1-7) levels.Results: Hemorrhagic shock induced renal tissue injury, increased the ACE and AT1R expressions, decreased the ACE2 and MasR expressions in kidney, accompanied by elevated Ang II and depressed Ang (1-7) in kidney. These adverse effects were partially reversed by MLDL or administrations of enalapril, Ang-(1-7), and losartan, respectively. In addition, the beneficial role of MLDL was reversed by ACE2 deficiency and Ang II or A-779 administrations. Conclusion: MLDL alleviates hemorrhagic shock-induced AKI in mice is related to the equilibrium ACE-AngII-AT1R and ACE2-Ang (1-7)-MasR axis.

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