Mechanism of the salutary effects of estrogen on Kupffer cell phagocytic capacity following trauma-hemorrhage: Pivotal role of Akt activation

Chi Hsun Hsieh, Eike A. Nickel, Jianguo Chen, Martin G Schwacha, Mashkoor A. Choudhry, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Kupffer cells are macrophages in the liver whose major role is to clear circulating pathogens. Decreased phagocytic capacity of Kupffer cells may result in severe systemic infection. We tested the hypothesis that the depressed Kupffer cell phagocytic capacity following trauma-hemorrhage is enhanced by estrogen administration and this occurs due to maintenance of Fc receptor expression and cellular ATP content via the activation of Akt. Male C3H/HeN mice were subjected to sham operation or trauma-hemorrhage and sacrificed 2 h thereafter. Estrogen, with or without an estrogen receptor antagonist (ICI 182,780), a PI3K inhibitor (Wortmannin), or vehicle, was injected during resuscitation. Kupffer cell phagocytic capacity was tested in vivo. The expression of Fc receptors, of Akt phosphorylation, of p38 MAPK phosphorylation, of DNA binding activity of NF-κB and ATP content of Kupffer cells were also determined. Trauma-hemorrhage suppressed Kupffer cell phagocytosis by decreasing Fc receptor expression and Akt activation; however, it induced p38 MAPK activation and increased NF-κB activity. Cellular ATP levels were also decreased following trauma-hemorrhage. Administration of estrogen following trauma-hemorrhage increased phospho-Akt levels and normalized all the parameters described as well as plasma levels of TNF-α, IL-6, and IL-10. Coadministration of ICI 182,780 or Wortmannin abolished the beneficial effects of estrogen in improving the phagocytic capacity of Kupffer cells following trauma-hemorrhage. Thus, activation of Akt plays a crucial role in mediating the salutary effect of estrogen in restoring trauma-hemorrhage-induced suppression of Kupffer cell phagocytosis.

Original languageEnglish (US)
Pages (from-to)4406-4414
Number of pages9
JournalJournal of Immunology
Volume182
Issue number7
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

Fingerprint

Kupffer Cells
Estrogens
Hemorrhage
Wounds and Injuries
Fc Receptors
Cytophagocytosis
Adenosine Triphosphate
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Inbred C3H Mouse
Phosphatidylinositol 3-Kinases
Resuscitation
Interleukin-10
Interleukin-6
Macrophages
Maintenance
Liver
DNA
Infection

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Mechanism of the salutary effects of estrogen on Kupffer cell phagocytic capacity following trauma-hemorrhage : Pivotal role of Akt activation. / Hsieh, Chi Hsun; Nickel, Eike A.; Chen, Jianguo; Schwacha, Martin G; Choudhry, Mashkoor A.; Bland, Kirby I.; Chaudry, Irshad H.

In: Journal of Immunology, Vol. 182, No. 7, 01.04.2009, p. 4406-4414.

Research output: Contribution to journalArticle

Hsieh, Chi Hsun ; Nickel, Eike A. ; Chen, Jianguo ; Schwacha, Martin G ; Choudhry, Mashkoor A. ; Bland, Kirby I. ; Chaudry, Irshad H. / Mechanism of the salutary effects of estrogen on Kupffer cell phagocytic capacity following trauma-hemorrhage : Pivotal role of Akt activation. In: Journal of Immunology. 2009 ; Vol. 182, No. 7. pp. 4406-4414.
@article{1ee02b85aa56498eaf05cc951ec5ff52,
title = "Mechanism of the salutary effects of estrogen on Kupffer cell phagocytic capacity following trauma-hemorrhage: Pivotal role of Akt activation",
abstract = "Kupffer cells are macrophages in the liver whose major role is to clear circulating pathogens. Decreased phagocytic capacity of Kupffer cells may result in severe systemic infection. We tested the hypothesis that the depressed Kupffer cell phagocytic capacity following trauma-hemorrhage is enhanced by estrogen administration and this occurs due to maintenance of Fc receptor expression and cellular ATP content via the activation of Akt. Male C3H/HeN mice were subjected to sham operation or trauma-hemorrhage and sacrificed 2 h thereafter. Estrogen, with or without an estrogen receptor antagonist (ICI 182,780), a PI3K inhibitor (Wortmannin), or vehicle, was injected during resuscitation. Kupffer cell phagocytic capacity was tested in vivo. The expression of Fc receptors, of Akt phosphorylation, of p38 MAPK phosphorylation, of DNA binding activity of NF-κB and ATP content of Kupffer cells were also determined. Trauma-hemorrhage suppressed Kupffer cell phagocytosis by decreasing Fc receptor expression and Akt activation; however, it induced p38 MAPK activation and increased NF-κB activity. Cellular ATP levels were also decreased following trauma-hemorrhage. Administration of estrogen following trauma-hemorrhage increased phospho-Akt levels and normalized all the parameters described as well as plasma levels of TNF-α, IL-6, and IL-10. Coadministration of ICI 182,780 or Wortmannin abolished the beneficial effects of estrogen in improving the phagocytic capacity of Kupffer cells following trauma-hemorrhage. Thus, activation of Akt plays a crucial role in mediating the salutary effect of estrogen in restoring trauma-hemorrhage-induced suppression of Kupffer cell phagocytosis.",
author = "Hsieh, {Chi Hsun} and Nickel, {Eike A.} and Jianguo Chen and Schwacha, {Martin G} and Choudhry, {Mashkoor A.} and Bland, {Kirby I.} and Chaudry, {Irshad H.}",
year = "2009",
month = "4",
day = "1",
doi = "10.4049/jimmunol.0803423",
language = "English (US)",
volume = "182",
pages = "4406--4414",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Mechanism of the salutary effects of estrogen on Kupffer cell phagocytic capacity following trauma-hemorrhage

T2 - Pivotal role of Akt activation

AU - Hsieh, Chi Hsun

AU - Nickel, Eike A.

AU - Chen, Jianguo

AU - Schwacha, Martin G

AU - Choudhry, Mashkoor A.

AU - Bland, Kirby I.

AU - Chaudry, Irshad H.

PY - 2009/4/1

Y1 - 2009/4/1

N2 - Kupffer cells are macrophages in the liver whose major role is to clear circulating pathogens. Decreased phagocytic capacity of Kupffer cells may result in severe systemic infection. We tested the hypothesis that the depressed Kupffer cell phagocytic capacity following trauma-hemorrhage is enhanced by estrogen administration and this occurs due to maintenance of Fc receptor expression and cellular ATP content via the activation of Akt. Male C3H/HeN mice were subjected to sham operation or trauma-hemorrhage and sacrificed 2 h thereafter. Estrogen, with or without an estrogen receptor antagonist (ICI 182,780), a PI3K inhibitor (Wortmannin), or vehicle, was injected during resuscitation. Kupffer cell phagocytic capacity was tested in vivo. The expression of Fc receptors, of Akt phosphorylation, of p38 MAPK phosphorylation, of DNA binding activity of NF-κB and ATP content of Kupffer cells were also determined. Trauma-hemorrhage suppressed Kupffer cell phagocytosis by decreasing Fc receptor expression and Akt activation; however, it induced p38 MAPK activation and increased NF-κB activity. Cellular ATP levels were also decreased following trauma-hemorrhage. Administration of estrogen following trauma-hemorrhage increased phospho-Akt levels and normalized all the parameters described as well as plasma levels of TNF-α, IL-6, and IL-10. Coadministration of ICI 182,780 or Wortmannin abolished the beneficial effects of estrogen in improving the phagocytic capacity of Kupffer cells following trauma-hemorrhage. Thus, activation of Akt plays a crucial role in mediating the salutary effect of estrogen in restoring trauma-hemorrhage-induced suppression of Kupffer cell phagocytosis.

AB - Kupffer cells are macrophages in the liver whose major role is to clear circulating pathogens. Decreased phagocytic capacity of Kupffer cells may result in severe systemic infection. We tested the hypothesis that the depressed Kupffer cell phagocytic capacity following trauma-hemorrhage is enhanced by estrogen administration and this occurs due to maintenance of Fc receptor expression and cellular ATP content via the activation of Akt. Male C3H/HeN mice were subjected to sham operation or trauma-hemorrhage and sacrificed 2 h thereafter. Estrogen, with or without an estrogen receptor antagonist (ICI 182,780), a PI3K inhibitor (Wortmannin), or vehicle, was injected during resuscitation. Kupffer cell phagocytic capacity was tested in vivo. The expression of Fc receptors, of Akt phosphorylation, of p38 MAPK phosphorylation, of DNA binding activity of NF-κB and ATP content of Kupffer cells were also determined. Trauma-hemorrhage suppressed Kupffer cell phagocytosis by decreasing Fc receptor expression and Akt activation; however, it induced p38 MAPK activation and increased NF-κB activity. Cellular ATP levels were also decreased following trauma-hemorrhage. Administration of estrogen following trauma-hemorrhage increased phospho-Akt levels and normalized all the parameters described as well as plasma levels of TNF-α, IL-6, and IL-10. Coadministration of ICI 182,780 or Wortmannin abolished the beneficial effects of estrogen in improving the phagocytic capacity of Kupffer cells following trauma-hemorrhage. Thus, activation of Akt plays a crucial role in mediating the salutary effect of estrogen in restoring trauma-hemorrhage-induced suppression of Kupffer cell phagocytosis.

UR - http://www.scopus.com/inward/record.url?scp=64249124099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64249124099&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0803423

DO - 10.4049/jimmunol.0803423

M3 - Article

C2 - 19299741

AN - SCOPUS:64249124099

VL - 182

SP - 4406

EP - 4414

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -