PMID- 8929555
OWN - NLM
STAT- MEDLINE
DCOM- 19961223
LR  - 20190516
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 60
IP  - 5
DP  - 1996 Nov
TI  - Endotoxin-inducible granulocyte-mediated hepatocytotoxicity requires adhesion and 
      serine protease release.
PG  - 633-43
AB  - In primary cultures of Kupffer cells and hepatocytes, human granulocytes 
      potentiated toxicity of endotoxin about 1000-fold. Granulocyte elastase activity 
      was found to correlate with toxicity. The serine protease inhibitors 
      alpha1-antitrypsin, eglin C, and aprotinin protected against toxicity. Tumor 
      necrosis factor-alpha (TNF-alpha) induced cytotoxicity and elastase release, 
      whereas neutralization of TNF-alpha blocked both events. We conclude that 
      TNF-alpha formed by Kupffer cells activates granulocytes. Experiments in cultures 
      where cells were separated by membranes permeable to mediators indicated that 
      cell contact is needed for toxicity. Scanning electron microscopy showed 
      granulocytes adhering to and interdigitating with hepatocytes. Using liver cells 
      from ICAM-1-deficient mice had no effect on toxicity. However, neutralizing CD31 
      inhibited toxicity and elastase release but not granulocyte adhesion. Our 
      findings demonstrate that adhesion of granulocytes is a necessary but not 
      sufficient condition for the synergistic interaction of endotoxin-stimulated 
      liver macrophages and granulocytes in the proteolytic killing of hepatocytes.
FAU - Sauer, A
AU  - Sauer A
AD  - Department of Biochemical Pharmacology, University of Konstanz, Federal Republic 
      of Germany.
FAU - Hartung, T
AU  - Hartung T
FAU - Aigner, J
AU  - Aigner J
FAU - Wendel, A
AU  - Wendel A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Androstadienes)
RN  - 0 (CD18 Antigens)
RN  - 0 (Endotoxins)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (Proteins)
RN  - 0 (Serpins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (alpha 1-Antitrypsin)
RN  - 0 (eglin proteinase inhibitors)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 9087-70-1 (Aprotinin)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Aprotinin/pharmacology
MH  - CD18 Antigens/analysis
MH  - Cell Adhesion
MH  - Cell Communication
MH  - Cell Membrane Permeability
MH  - Cells, Cultured
MH  - Chemical and Drug Induced Liver Injury/etiology/*physiopathology
MH  - Coculture Techniques
MH  - Endotoxins/pharmacology/*toxicity
MH  - Granulocytes/*drug effects/enzymology/metabolism/ultrastructure
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/physiology
MH  - Kupffer Cells/*metabolism
MH  - Liver/cytology/*drug effects
MH  - Liver Failure/*chemically induced/etiology/physiopathology
MH  - Male
MH  - Mice
MH  - Microscopy, Electron, Scanning
MH  - Pancreatic Elastase/antagonists & inhibitors/*metabolism
MH  - Platelet Endothelial Cell Adhesion Molecule-1/analysis
MH  - Proteins
MH  - Rats
MH  - Rats, Inbred F344
MH  - Serine Endopeptidases/*metabolism
MH  - Serpins/pharmacology
MH  - Shock, Septic/complications
MH  - Tumor Necrosis Factor-alpha/metabolism/*physiology
MH  - Wortmannin
MH  - alpha 1-Antitrypsin/pharmacology
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
AID - 10.1002/jlb.60.5.633 [doi]
PST - ppublish
SO  - J Leukoc Biol. 1996 Nov;60(5):633-43. doi: 10.1002/jlb.60.5.633.