Osmotic Regulation of Cell Function and Possible Clinical Applications

Shukla, Alok; Hashiguchi, Naoyuki; Chen, Yu; Coimbra, Raúl; Hoyt, David B.; Junger, Wolfgang G.

doi:10.1097/00024382-200405000-00001

Cited by 72 publications

(56 citation statements)

References 152 publications

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“…Multiple injuries and major hemorrhage induce marked dysregulation of the systemic immune response, end organ damage, and death (33)(34)(35)(36)(37)(38). In patients with multiple injuries who are at risk for infectious complications, outcome is believed to be determined by the interrelationship of various inflamma- Genomic and nongenomic effects of estrogen.…”

Section: Sex Dichotomy In Trauma Outcomementioning

confidence: 99%

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

Raju

Bland

Chaudry

2008

Mol Med

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ESTROGEN, MECHANISM OF ACTIONE2, the female hormone, is mainly produced by the ovaries and the placenta. The three major estrogens in women are estradiol, estriol, and estrone ( Figure 1). Estrogens are synthesized from androgens by the loss of C-19 angular methyl group and the formation of an aromatic A ring. Whereas estradiol is derived from testosterone, estrone is derived from androstenedione. The main form of E2 in women Trauma-hemorrhage leads to prolonged immune suppression, sepsis, and multiple organ failure. The condition affects all compartments of the immune system, and extensive studies have been carried out elucidating the immunological events following trauma-hemorrhage. The immune alteration observed following trauma-hemorrhage is gender dependent in both animal models and humans, though some studies in humans are contradictory. Within 30 min after trauma-hemorrhage, splenic and peritoneal macrophages, as well as T-cell function, are depressed in male animals, but not in proestrus females. Studies have also shown that the survival rate and the induction of subsequent sepsis following trauma-hemorrhage are significantly higher in males and ovariectomized females compared with proestrus females. These and other investigations show that sex hormones form the basis of this gender dichotomy, and administration of estrogen can ameliorate the immune depression and increase the survival rate after trauma-hemorrhage. This review specifically elaborates the studies carried out thus far demonstrating immunological alteration after trauma-hemorrhage and its modulation by estrogen. Also, estrogen was shown to produce its salutary effects through nuclear as well as extranuclear receptors. Estrogen rapidly activates several protein kinases and phosphatases, as well as the release of calcium in different cell types. The results of the studies exemplify the promise of estrogen as a therapeutic adjunct in treating adverse pathophysiological conditions following trauma-hemorrhage.

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Section: Sex Dichotomy In Trauma Outcomementioning

confidence: 99%

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

Raju

Bland

Chaudry

2008

Mol Med

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“…The impairment in host defense following trauma could result from a defect in cellmediated immune responses (3,4) and impaired microbicidal activity by cells of the innate immune system. A number of studies have demonstrated that trauma-hemorrhage (T-H) 3 induces a marked alteration of many immune functions, including T cell activation, proliferation and cytokine release, macrophage Ag presentation function, and cytokine release (5)(6)(7)(8)(9). Furthermore, our previous studies have shown that following hemorrhage, splenic macrophage, peritoneal macrophage, and Kupffer cell Ag-presenting capacity are depressed, and this depression is associated with decreased MHC class II expression (10,11).…”

Section: T Is Well Known That Traumatic Injury-induced Immunosup-mentioning

confidence: 99%

Trauma-Hemorrhage Induces Depressed Splenic Dendritic Cell Functions in Mice

Kawasaki

Hubbard

Choudhry

et al. 2006

The Journal of Immunology

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Although Kupffer cell, splenic, and peritoneal macrophage functions are markedly altered following trauma-hemorrhage (T-H), it remains unclear whether T-H also affects splenic dendritic cell (sDC) functions. We hypothesized that sDC functions will also be compromised following T-H. Male C3H/HeN (6- to 8-wk) mice were randomly assigned to sham operation or T-H. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (four times the shed blood volume in the form of Ringer’s lactate). Two hours later, the mice were sacrificed; sDC were isolated; and the changes in their apoptosis, MHC class II expression, and ability to produce costimulatory cytokines and Ag presentation were measured. The results indicate that sDC Ag presentation capacity was significantly decreased and MHC class II expression was also significantly decreased following T-H. Moreover, LPS-induced IL-12 production and LPS- or IL-12-induced IFN-γ production following T-H were significantly decreased. Thus, the markedly decreased MHC class II expression and cytokine (IL-12, IFN-γ) production following T-H may be the cause for the depressed sDC Ag presentation under those conditions. This depression in Ag presentation could contribute to the host’s enhanced susceptibility to sepsis following T-H.

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“…Many studies have demonstrated that trauma-hemorrhage induces marked alterations in various immune functions (Meldrum et al, 1997;Murphy et al, 2005;Murphy et al, 2004;Noel et al, 2005;Shukla et al, 2004;Zuckerbraun et al, 2005). Severe hemorrhage followed by adequate resuscitation with blood and crystalloid solutions is known to produce depression of immune system, such as lymphocyte functions and macrophage functions (Chaudry and Ayala, 1993).…”

Section: Introductionmentioning

confidence: 99%

17β-Estradiol's salutary effects on splenic dendritic cell functions following trauma–hemorrhage are mediated via estrogen receptor-α

Kawasaki

Choudhry

Suzuki

et al. 2008

Molecular Immunology

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Although 17β-estradiol administration following trauma-hemorrhage attenuates Kupffer cell, splenic and peritoneal macrophage functions, it remains unknown whether 17β-estradiol has any salutary effects on splenic dendritic cell (DC) functions and if so, whether such effects are mediated via the estrogen receptors (ER). We hypothesized that 17β-estradiol administration following traumahemorrhage has salutary effects on splenic DC functions. Male C3H/HeN (6-8 weeks) mice were randomly assigned to sham operation or trauma-hemorrhage. Trauma-hemorrhage was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure [BP] 35 mmHg), followed by fluid resuscitation (4 × the shed blood volume in the form of Ringer's lactate). Estrogen receptor (ER)-α agonist propyl pyrazole triol (PPT; 5 μg/kg), ER-β agonist diarylpropionitrile (DPN; 5μg/ kg), 17β-estradiol (50 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Two hrs later, the mice were sacrificed, splenic DCs were isolated and the changes in their apoptosis, co-stimulating factors and MHC class II expression, ability to produce cytokines, and antigen presentation capacity were measured. Apoptosis of splenic DC increased following trauma-hemorrhage; however, 17β-estradiol administration after trauma-hemorrhage normalized the rate of apoptosis. Moreover, splenic DC cytokines production, co-stimulating factors and MHC class II expression, and antigen presentation capacity were significantly decreased following traumahemorrhage; however, 17β-estradiol as well as PPT also prevented these depressions. In contrast, DPN did not attenuate splenic DC functions following trauma-hemorrhage. Since PPT administration following trauma-hemorrhage was more effective in normalizing splenic DC functions than DPN, the salutary effects of 17β-estradiol on splenic DC functions are mediated predominantly via ER-α.

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Osmotic Regulation of Cell Function and Possible Clinical Applications

Cited by 72 publications

References 152 publications

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

Estrogen: A Novel Therapeutic Adjunct for the Treatment of Trauma-Hemorrhage—Induced Immunological Alterations

Trauma-Hemorrhage Induces Depressed Splenic Dendritic Cell Functions in Mice

17β-Estradiol's salutary effects on splenic dendritic cell functions following trauma–hemorrhage are mediated via estrogen receptor-α

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