Altered Kupffer cell function in biliary obstruction

Rebecca M. Minter, Ming Hui Fan, Jianmin Sun, Andreas Niederbichler, Kyros Ipaktchi, Saman Arbabi, Mark R. Hemmila, Daniel G. Remick, Stewart C. Wang, Grace L. Su

Research output: Contribution to journalArticle

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Abstract

Background. An altered Kupffer cell (KC) response is thought to be responsible for the characteristic phenotype observed after biliary obstruction: a phenotype marked by a defect in the hepatic reticuloendothelial system and a hypersensitivity to endotoxin. Few studies, however, have directly examined KC function. We have sought to define the specific alterations in function and phenotype that occur in the KC after biliary obstruction. Methods. KCs were isolated from female C57BL/6 mice 4 days after a sham or common bile duct ligation (CBDL) operation. Phagocytosis, oxidative burst potential, and intracellular bacterial killing were measured as markers of reticuloendothelial system function. The KC response to endotoxin was assessed by measuring tumor necrosis factor alpha and interleukin 6 levels in the media after stimulation with lipopolysaccharide (LPS) or with LPS plus LPS-binding protein (LBP). Results. CBDL KCs demonstrated a significant increase in phagocytic ability and significantly decreased baseline oxidative stress, compared with Shams. The oxidative burst potential, however, was equivalent or higher for CBDL KCs. CBDL KCs also demonstrated increased numbers of viable intracellular bacteria after infection; however, it is unclear if this finding represents impaired intracellular bacterial killing or increased phagocytosis of bacteria. With respect to the KC response to endotoxin, CBDL KCs were found to be less sensitive to the stimulatory effects of LPS alone but were exquisitely sensitive to the effects of LBP. LBP levels were found to be significantly elevated in CBDL animals, and CBDL KCs demonstrated a dose-dependent, exaggerated tumor necrosis factor alpha and interleukin 6 response to LPS administered with LBP. Conclusions. KC function is clearly altered after biliary obstruction. Phagocytic ability is actually increased, although the ability of CBDL KCs to kill bacteria within the phagosome remains ill defined. CBDL KCs are exquisitely sensitive to the effects of LBP, and LBP levels are elevated after biliary obstruction. LBP may be responsible for the increased proinflammatory response observed after endotoxin challenge in animals with biliary obstruction.

Original languageEnglish (US)
Pages (from-to)236-245
Number of pages10
JournalSurgery
Volume138
Issue number2
DOIs
StatePublished - Aug 1 2005

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Kupffer Cells
Common Bile Duct
Ligation
Endotoxins
Lipopolysaccharides
Mononuclear Phagocyte System
Respiratory Burst
Bacteria
Phenotype
Phagocytosis
Interleukin-6
Tumor Necrosis Factor-alpha
Phagosomes
lipopolysaccharide-binding protein
Inbred C57BL Mouse
Protein Binding
Hypersensitivity
Oxidative Stress
Liver

ASJC Scopus subject areas

  • Surgery

Cite this

Minter, R. M., Fan, M. H., Sun, J., Niederbichler, A., Ipaktchi, K., Arbabi, S., ... Su, G. L. (2005). Altered Kupffer cell function in biliary obstruction. Surgery, 138(2), 236-245. https://doi.org/10.1016/j.surg.2005.04.001

Altered Kupffer cell function in biliary obstruction. / Minter, Rebecca M.; Fan, Ming Hui; Sun, Jianmin; Niederbichler, Andreas; Ipaktchi, Kyros; Arbabi, Saman; Hemmila, Mark R.; Remick, Daniel G.; Wang, Stewart C.; Su, Grace L.

In: Surgery, Vol. 138, No. 2, 01.08.2005, p. 236-245.

Research output: Contribution to journalArticle

Minter, RM, Fan, MH, Sun, J, Niederbichler, A, Ipaktchi, K, Arbabi, S, Hemmila, MR, Remick, DG, Wang, SC & Su, GL 2005, 'Altered Kupffer cell function in biliary obstruction', Surgery, vol. 138, no. 2, pp. 236-245. https://doi.org/10.1016/j.surg.2005.04.001
Minter RM, Fan MH, Sun J, Niederbichler A, Ipaktchi K, Arbabi S et al. Altered Kupffer cell function in biliary obstruction. Surgery. 2005 Aug 1;138(2):236-245. https://doi.org/10.1016/j.surg.2005.04.001
Minter, Rebecca M. ; Fan, Ming Hui ; Sun, Jianmin ; Niederbichler, Andreas ; Ipaktchi, Kyros ; Arbabi, Saman ; Hemmila, Mark R. ; Remick, Daniel G. ; Wang, Stewart C. ; Su, Grace L. / Altered Kupffer cell function in biliary obstruction. In: Surgery. 2005 ; Vol. 138, No. 2. pp. 236-245.
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abstract = "Background. An altered Kupffer cell (KC) response is thought to be responsible for the characteristic phenotype observed after biliary obstruction: a phenotype marked by a defect in the hepatic reticuloendothelial system and a hypersensitivity to endotoxin. Few studies, however, have directly examined KC function. We have sought to define the specific alterations in function and phenotype that occur in the KC after biliary obstruction. Methods. KCs were isolated from female C57BL/6 mice 4 days after a sham or common bile duct ligation (CBDL) operation. Phagocytosis, oxidative burst potential, and intracellular bacterial killing were measured as markers of reticuloendothelial system function. The KC response to endotoxin was assessed by measuring tumor necrosis factor alpha and interleukin 6 levels in the media after stimulation with lipopolysaccharide (LPS) or with LPS plus LPS-binding protein (LBP). Results. CBDL KCs demonstrated a significant increase in phagocytic ability and significantly decreased baseline oxidative stress, compared with Shams. The oxidative burst potential, however, was equivalent or higher for CBDL KCs. CBDL KCs also demonstrated increased numbers of viable intracellular bacteria after infection; however, it is unclear if this finding represents impaired intracellular bacterial killing or increased phagocytosis of bacteria. With respect to the KC response to endotoxin, CBDL KCs were found to be less sensitive to the stimulatory effects of LPS alone but were exquisitely sensitive to the effects of LBP. LBP levels were found to be significantly elevated in CBDL animals, and CBDL KCs demonstrated a dose-dependent, exaggerated tumor necrosis factor alpha and interleukin 6 response to LPS administered with LBP. Conclusions. KC function is clearly altered after biliary obstruction. Phagocytic ability is actually increased, although the ability of CBDL KCs to kill bacteria within the phagosome remains ill defined. CBDL KCs are exquisitely sensitive to the effects of LBP, and LBP levels are elevated after biliary obstruction. LBP may be responsible for the increased proinflammatory response observed after endotoxin challenge in animals with biliary obstruction.",
author = "Minter, {Rebecca M.} and Fan, {Ming Hui} and Jianmin Sun and Andreas Niederbichler and Kyros Ipaktchi and Saman Arbabi and Hemmila, {Mark R.} and Remick, {Daniel G.} and Wang, {Stewart C.} and Su, {Grace L.}",
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AU - Fan, Ming Hui

AU - Sun, Jianmin

AU - Niederbichler, Andreas

AU - Ipaktchi, Kyros

AU - Arbabi, Saman

AU - Hemmila, Mark R.

AU - Remick, Daniel G.

AU - Wang, Stewart C.

AU - Su, Grace L.

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N2 - Background. An altered Kupffer cell (KC) response is thought to be responsible for the characteristic phenotype observed after biliary obstruction: a phenotype marked by a defect in the hepatic reticuloendothelial system and a hypersensitivity to endotoxin. Few studies, however, have directly examined KC function. We have sought to define the specific alterations in function and phenotype that occur in the KC after biliary obstruction. Methods. KCs were isolated from female C57BL/6 mice 4 days after a sham or common bile duct ligation (CBDL) operation. Phagocytosis, oxidative burst potential, and intracellular bacterial killing were measured as markers of reticuloendothelial system function. The KC response to endotoxin was assessed by measuring tumor necrosis factor alpha and interleukin 6 levels in the media after stimulation with lipopolysaccharide (LPS) or with LPS plus LPS-binding protein (LBP). Results. CBDL KCs demonstrated a significant increase in phagocytic ability and significantly decreased baseline oxidative stress, compared with Shams. The oxidative burst potential, however, was equivalent or higher for CBDL KCs. CBDL KCs also demonstrated increased numbers of viable intracellular bacteria after infection; however, it is unclear if this finding represents impaired intracellular bacterial killing or increased phagocytosis of bacteria. With respect to the KC response to endotoxin, CBDL KCs were found to be less sensitive to the stimulatory effects of LPS alone but were exquisitely sensitive to the effects of LBP. LBP levels were found to be significantly elevated in CBDL animals, and CBDL KCs demonstrated a dose-dependent, exaggerated tumor necrosis factor alpha and interleukin 6 response to LPS administered with LBP. Conclusions. KC function is clearly altered after biliary obstruction. Phagocytic ability is actually increased, although the ability of CBDL KCs to kill bacteria within the phagosome remains ill defined. CBDL KCs are exquisitely sensitive to the effects of LBP, and LBP levels are elevated after biliary obstruction. LBP may be responsible for the increased proinflammatory response observed after endotoxin challenge in animals with biliary obstruction.

AB - Background. An altered Kupffer cell (KC) response is thought to be responsible for the characteristic phenotype observed after biliary obstruction: a phenotype marked by a defect in the hepatic reticuloendothelial system and a hypersensitivity to endotoxin. Few studies, however, have directly examined KC function. We have sought to define the specific alterations in function and phenotype that occur in the KC after biliary obstruction. Methods. KCs were isolated from female C57BL/6 mice 4 days after a sham or common bile duct ligation (CBDL) operation. Phagocytosis, oxidative burst potential, and intracellular bacterial killing were measured as markers of reticuloendothelial system function. The KC response to endotoxin was assessed by measuring tumor necrosis factor alpha and interleukin 6 levels in the media after stimulation with lipopolysaccharide (LPS) or with LPS plus LPS-binding protein (LBP). Results. CBDL KCs demonstrated a significant increase in phagocytic ability and significantly decreased baseline oxidative stress, compared with Shams. The oxidative burst potential, however, was equivalent or higher for CBDL KCs. CBDL KCs also demonstrated increased numbers of viable intracellular bacteria after infection; however, it is unclear if this finding represents impaired intracellular bacterial killing or increased phagocytosis of bacteria. With respect to the KC response to endotoxin, CBDL KCs were found to be less sensitive to the stimulatory effects of LPS alone but were exquisitely sensitive to the effects of LBP. LBP levels were found to be significantly elevated in CBDL animals, and CBDL KCs demonstrated a dose-dependent, exaggerated tumor necrosis factor alpha and interleukin 6 response to LPS administered with LBP. Conclusions. KC function is clearly altered after biliary obstruction. Phagocytic ability is actually increased, although the ability of CBDL KCs to kill bacteria within the phagosome remains ill defined. CBDL KCs are exquisitely sensitive to the effects of LBP, and LBP levels are elevated after biliary obstruction. LBP may be responsible for the increased proinflammatory response observed after endotoxin challenge in animals with biliary obstruction.

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