PMID- 16936255
OWN - NLM
STAT- MEDLINE
DCOM- 20061024
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 169
IP  - 3
DP  - 2006 Sep
TI  - Kupffer cells and their mediators: the culprits in producing distant organ damage 
      after trauma-hemorrhage.
PG  - 784-94
AB  - Posttraumatic activation of macrophages enhances development of systemic 
      inflammation/immunosuppression and organ dysfunction. We hypothesized that 
      Kupffer cells are the main source of monocyte chemoattractant protein-1 (MCP-1) 
      production after trauma-hemorrhage, that administration of 17beta-estradiol (E2) 
      after trauma-hemorrhage modulates MCP-1 release and reduces remote organ damage, 
      and that salutary effects of E2 are mediated via estrogen receptor (ER)-alpha. To 
      test these hypotheses, female B57BL/J6 mice received E2 (50 microg/25 g) or 
      vehicle after trauma-hemorrhage and female 129 Sve ER-beta-/- transgenic mice and 
      ovariectomized wild-type mice received E2 or ER-alpha agonist propyl pyrazole 
      triol (50 microg/25 g) after trauma-hemorrhage. Systemic MCP-1 and interleukin-6 
      and their release by liver, spleen, and lung macrophages were determined by flow 
      cytometry 4 hours after trauma-hemorrhage. Prior Kupffer cell depletion with 
      gadolinium chloride significantly decreased systemic MCP-1 and interleukin-6 
      after trauma-hemorrhage and was associated with decreased edema/neutrophil 
      infiltration in lung and liver. Kupffer cells were the only macrophages showing 
      significant MCP-1 release, which was markedly reduced by E2 or propyl pyrazole 
      triol in wild-type and in ER-beta-/- mice. Pretreatment of mice with anti-MCP-1 
      antiserum prevented an increase in myeloperoxidase and edema in lung and liver. 
      These findings suggest that Kupffer cell-derived MCP-1 plays a major role in 
      remote organ dysfunction after trauma-hemorrhage.
FAU - Hildebrand, Frank
AU  - Hildebrand F
AD  - Center for Surgical Research and Department of Surgery, University of Alabama at 
      Birmingham, Volker Hall G094, 1670 University Blvd., Birmingham, AL 35294-0019, 
      USA.
FAU - Hubbard, William J
AU  - Hubbard WJ
FAU - Choudhry, Mashkoor A
AU  - Choudhry MA
FAU - Frink, Michael
AU  - Frink M
FAU - Pape, Hans-Christoph
AU  - Pape HC
FAU - Kunkel, Steven L
AU  - Kunkel SL
FAU - Chaudry, Irshad H
AU  - Chaudry IH
LA  - eng
GR  - R01 GM037127/GM/NIGMS NIH HHS/United States
GR  - R01 GM37127/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Phenols)
RN  - 0 (Pyrazoles)
RN  - 0T83Y6JZPF (4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol)
RN  - 4TI98Z838E (Estradiol)
RN  - AU0V1LM3JT (Gadolinium)
RN  - P7082WY76D (gadolinium chloride)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Antibodies/immunology/pharmacology
MH  - Chemokine CCL2/immunology
MH  - Estradiol/pharmacology
MH  - Estrogen Receptor beta/agonists/deficiency/*immunology
MH  - Female
MH  - Gadolinium/pharmacology
MH  - Hemorrhage/*immunology/pathology
MH  - Interleukin-6/immunology
MH  - Kupffer Cells/*immunology/pathology
MH  - Liver/immunology/pathology
MH  - Lung/immunology/pathology
MH  - Macrophage Activation/drug effects/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Neutrophil Infiltration/drug effects/immunology
MH  - Phenols
MH  - Pulmonary Edema/*immunology/pathology
MH  - Pyrazoles/pharmacology
MH  - Spleen/immunology/pathology
MH  - Wounds and Injuries/*immunology/pathology
PMC - PMC1698811
EDAT- 2006/08/29 09:00
MHDA- 2006/10/25 09:00
PMCR- 2007/03/01
CRDT- 2006/08/29 09:00
PHST- 2006/08/29 09:00 [pubmed]
PHST- 2006/10/25 09:00 [medline]
PHST- 2006/08/29 09:00 [entrez]
PHST- 2007/03/01 00:00 [pmc-release]
AID - S0002-9440(10)62757-5 [pii]
AID - 10.2353/ajpath.2006.060010 [doi]
PST - ppublish
SO  - Am J Pathol. 2006 Sep;169(3):784-94. doi: 10.2353/ajpath.2006.060010.