Role of neutrophils and Kupffer cells in hepatic cells in hepatic infection: Do we have it wrong?

[Guest guest]

Journal of Surgical Research

Volume 121, Issue 2 , October 2004, Page 333

doi:10.1016/j.jss.2004.07.214

Copyright © 2001 Elsevier Inc. All rights reserved.

Abstract

Role of neutrophils and Kupffer cells in hepatic cells in hepatic infection:

Do we have it wrong?

D. R. Jeyarajah MDa, M. L. Kielar MDa, X. Zhou MDa, P. Karimi MDa, N. L.

Frantz BAa and C. Y. Lu MDa

a Southwestern Medical School, USA

Available online 20 October 2004.

Abstract

Introduction. Systemic infection is localized and cleared by the liver

within minutes. Kupffer cells (KCs) are thought to be the critical cell

involved in bacterial clearance. Work in this field has been performed with

Listeria Monocytogenes, an intracellular pathogen that is not seen often in

the clinical setting. This work examines the role of KCs and neutrophils in

hepatic clearance of E. coli, an organism that frequently causes sepsis.

Methods. C57BL/6 mice were rendered KC-deficient with Gadolinium chloride

(Gd) or neutropenic with anti-Ly6 monoclonal antibody therapy. KC depletion

was confirmed by demonstrating decreased uptake of colloidal carbon, an

agent taken up by KCs, or by immunohistochemistry using F4/80 mAb. Control

animals received PBS injection. Specific hepatic infection with various

doses (2 × 105-106) of E. coli was performed by direct injection into the

portal vein (PV). Colony counts (CFU) recovered from the liver and

peripheral blood, and histology of the liver, were assessed at 10 min and 6

h after infection (n = 4/grp). Survival was assessed in neutropenic animals

(n = 8/grp). Results. KC depletion did not result in alterations of trapping

(at 10 min) or clearance of E. coli in the liver, as measured by bacterial

growth. Depletion of neutrophils resulted in similar trapping, but

significantly greater bacterial growth by 6 h after infection. Similarly,

neutropenia resulted in decreased survival after infection (25% survival

neutropenic/100% survival in neutrophil sufficient). Histologic examination

revealed the presence of large clusters of neutrophils in KC-depleted

animals, but not KC-sufficient animals, at 6 h after infection, suggesting a

role for KCs in control of activated neutrophils that are involved in

clearance of infection. Conclusions. Surprisingly, KCs appear not to be

critical to initial trapping or control of E. coli; by comparison,

neutrophils are critical to the elimination of E. coli. KCs are likely

important in controlling neutrophils that have emigrated to the liver to

control infection.

[Guest guest]

Journal of Surgical Research

Volume 121, Issue 2 , October 2004, Page 333

doi:10.1016/j.jss.2004.07.214

Copyright © 2001 Elsevier Inc. All rights reserved.

Abstract

Role of neutrophils and Kupffer cells in hepatic cells in hepatic infection:

Do we have it wrong?

D. R. Jeyarajah MDa, M. L. Kielar MDa, X. Zhou MDa, P. Karimi MDa, N. L.

Frantz BAa and C. Y. Lu MDa

a Southwestern Medical School, USA

Available online 20 October 2004.

Abstract

Introduction. Systemic infection is localized and cleared by the liver

within minutes. Kupffer cells (KCs) are thought to be the critical cell

involved in bacterial clearance. Work in this field has been performed with

Listeria Monocytogenes, an intracellular pathogen that is not seen often in

the clinical setting. This work examines the role of KCs and neutrophils in

hepatic clearance of E. coli, an organism that frequently causes sepsis.

Methods. C57BL/6 mice were rendered KC-deficient with Gadolinium chloride

(Gd) or neutropenic with anti-Ly6 monoclonal antibody therapy. KC depletion

was confirmed by demonstrating decreased uptake of colloidal carbon, an

agent taken up by KCs, or by immunohistochemistry using F4/80 mAb. Control

animals received PBS injection. Specific hepatic infection with various

doses (2 × 105-106) of E. coli was performed by direct injection into the

portal vein (PV). Colony counts (CFU) recovered from the liver and

peripheral blood, and histology of the liver, were assessed at 10 min and 6

h after infection (n = 4/grp). Survival was assessed in neutropenic animals

(n = 8/grp). Results. KC depletion did not result in alterations of trapping

(at 10 min) or clearance of E. coli in the liver, as measured by bacterial

growth. Depletion of neutrophils resulted in similar trapping, but

significantly greater bacterial growth by 6 h after infection. Similarly,

neutropenia resulted in decreased survival after infection (25% survival

neutropenic/100% survival in neutrophil sufficient). Histologic examination

revealed the presence of large clusters of neutrophils in KC-depleted

animals, but not KC-sufficient animals, at 6 h after infection, suggesting a

role for KCs in control of activated neutrophils that are involved in

clearance of infection. Conclusions. Surprisingly, KCs appear not to be

critical to initial trapping or control of E. coli; by comparison,

neutrophils are critical to the elimination of E. coli. KCs are likely

important in controlling neutrophils that have emigrated to the liver to

control infection.

[Guest guest]

Journal of Surgical Research

Volume 121, Issue 2 , October 2004, Page 333

doi:10.1016/j.jss.2004.07.214

Copyright © 2001 Elsevier Inc. All rights reserved.

Abstract

Role of neutrophils and Kupffer cells in hepatic cells in hepatic infection:

Do we have it wrong?

D. R. Jeyarajah MDa, M. L. Kielar MDa, X. Zhou MDa, P. Karimi MDa, N. L.

Frantz BAa and C. Y. Lu MDa

a Southwestern Medical School, USA

Available online 20 October 2004.

Abstract

Introduction. Systemic infection is localized and cleared by the liver

within minutes. Kupffer cells (KCs) are thought to be the critical cell

involved in bacterial clearance. Work in this field has been performed with

Listeria Monocytogenes, an intracellular pathogen that is not seen often in

the clinical setting. This work examines the role of KCs and neutrophils in

hepatic clearance of E. coli, an organism that frequently causes sepsis.

Methods. C57BL/6 mice were rendered KC-deficient with Gadolinium chloride

(Gd) or neutropenic with anti-Ly6 monoclonal antibody therapy. KC depletion

was confirmed by demonstrating decreased uptake of colloidal carbon, an

agent taken up by KCs, or by immunohistochemistry using F4/80 mAb. Control

animals received PBS injection. Specific hepatic infection with various

doses (2 × 105-106) of E. coli was performed by direct injection into the

portal vein (PV). Colony counts (CFU) recovered from the liver and

peripheral blood, and histology of the liver, were assessed at 10 min and 6

h after infection (n = 4/grp). Survival was assessed in neutropenic animals

(n = 8/grp). Results. KC depletion did not result in alterations of trapping

(at 10 min) or clearance of E. coli in the liver, as measured by bacterial

growth. Depletion of neutrophils resulted in similar trapping, but

significantly greater bacterial growth by 6 h after infection. Similarly,

neutropenia resulted in decreased survival after infection (25% survival

neutropenic/100% survival in neutrophil sufficient). Histologic examination

revealed the presence of large clusters of neutrophils in KC-depleted

animals, but not KC-sufficient animals, at 6 h after infection, suggesting a

role for KCs in control of activated neutrophils that are involved in

clearance of infection. Conclusions. Surprisingly, KCs appear not to be

critical to initial trapping or control of E. coli; by comparison,

neutrophils are critical to the elimination of E. coli. KCs are likely

important in controlling neutrophils that have emigrated to the liver to

control infection.

[Guest guest]

Journal of Surgical Research

Volume 121, Issue 2 , October 2004, Page 333

doi:10.1016/j.jss.2004.07.214

Copyright © 2001 Elsevier Inc. All rights reserved.

Abstract

Role of neutrophils and Kupffer cells in hepatic cells in hepatic infection:

Do we have it wrong?

D. R. Jeyarajah MDa, M. L. Kielar MDa, X. Zhou MDa, P. Karimi MDa, N. L.

Frantz BAa and C. Y. Lu MDa

a Southwestern Medical School, USA

Available online 20 October 2004.

Abstract

Introduction. Systemic infection is localized and cleared by the liver

within minutes. Kupffer cells (KCs) are thought to be the critical cell

involved in bacterial clearance. Work in this field has been performed with

Listeria Monocytogenes, an intracellular pathogen that is not seen often in

the clinical setting. This work examines the role of KCs and neutrophils in

hepatic clearance of E. coli, an organism that frequently causes sepsis.

Methods. C57BL/6 mice were rendered KC-deficient with Gadolinium chloride

(Gd) or neutropenic with anti-Ly6 monoclonal antibody therapy. KC depletion

was confirmed by demonstrating decreased uptake of colloidal carbon, an

agent taken up by KCs, or by immunohistochemistry using F4/80 mAb. Control

animals received PBS injection. Specific hepatic infection with various

doses (2 × 105-106) of E. coli was performed by direct injection into the

portal vein (PV). Colony counts (CFU) recovered from the liver and

peripheral blood, and histology of the liver, were assessed at 10 min and 6

h after infection (n = 4/grp). Survival was assessed in neutropenic animals

(n = 8/grp). Results. KC depletion did not result in alterations of trapping

(at 10 min) or clearance of E. coli in the liver, as measured by bacterial

growth. Depletion of neutrophils resulted in similar trapping, but

significantly greater bacterial growth by 6 h after infection. Similarly,

neutropenia resulted in decreased survival after infection (25% survival

neutropenic/100% survival in neutrophil sufficient). Histologic examination

revealed the presence of large clusters of neutrophils in KC-depleted

animals, but not KC-sufficient animals, at 6 h after infection, suggesting a

role for KCs in control of activated neutrophils that are involved in

clearance of infection. Conclusions. Surprisingly, KCs appear not to be

critical to initial trapping or control of E. coli; by comparison,

neutrophils are critical to the elimination of E. coli. KCs are likely

important in controlling neutrophils that have emigrated to the liver to

control infection.