PMID- 9731570
OWN - NLM
STAT- MEDLINE
DCOM- 19980917
LR  - 20171116
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 28
IP  - 3
DP  - 1998 Sep
TI  - Parenchymal cell apoptosis as a signal for sinusoidal sequestration and 
      transendothelial migration of neutrophils in murine models of endotoxin and 
      Fas-antibody-induced liver injury.
PG  - 761-7
AB  - Endotoxin (ET) induces neutrophil sequestration in hepatic sinusoids, the 
      activation of proinflammatory transcription factors (nuclear factor KB 
      [NF-kappaB]) with up-regulation of adhesion molecules on sinusoidal endothelial 
      cells and hepatocytes. However, if galactosamine (Gal) is co-administered with 
      ET, neutrophils transmigrate and attack parenchymal cells. This suggests that a 
      signal from parenchymal cells triggers neutrophil transmigration. In this study, 
      we tested the hypothesis that parenchymal cell apoptosis may induce neutrophil 
      transendothelial migration in the Gal/ET model. Treatment of C3Heb/FeJ mice with 
      700 mg/kg Gal and 100 microg/kg ET induced tumor necrosis factor alpha 
      (TNF-alpha) formation (13.25 +/- 0.75 ng/mL) and hepatic NF-kappaB activation at 
      90 minutes; the generation of the C-X-C chemokine KC (2.86 +/- 0.30 ng/mL at 5 
      hours); sinusoidal neutrophil sequestration (380 +/- 21 polymorphonuclear 
      leukocytes/50 high-power fields) and apoptosis (925% +/- 29% increase of DNA 
      fragmentation; and a 45-fold increase of terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL)-positive cells) at 6 hours, 
      followed by transmigration of neutrophils and development of substantial necrosis 
      (38% +/- 3% of hepatocytes; alanine transaminase [ALT]: 1,500 +/- 300 U/L) at 7 
      hours. Administration of uridine (1,000 mg/kg) did not reduce plasma levels of 
      TNF-alpha and KC, NF-kappaB activation, or polymorphonuclear leukocyte 
      sequestration, but attenuated apoptosis by 90% to 94%. In these livers, 
      neutrophils did not transmigrate and liver injury was prevented (necrosis: < 5%; 
      ALT: 40 +/- 3 U/L). However, massive apoptosis and liver injury initiated by the 
      anti-Fas antibody, Jo2, did not recruit neutrophils into the liver. We conclude 
      that excessive parenchymal cell apoptosis represents an important signal for 
      transmigration of primed neutrophils sequestered in sinusoids during endotoxemia 
      in vivo. However, apoptosis per se does not cause neutrophil sequestration in the 
      liver vasculature.
FAU - Lawson, J A
AU  - Lawson JA
AD  - Department of Pharmacology, Pharmacia and Upjohn, Inc., Kalamazoo, MI 49007, USA.
FAU - Fisher, M A
AU  - Fisher MA
FAU - Simmons, C A
AU  - Simmons CA
FAU - Farhood, A
AU  - Farhood A
FAU - Jaeschke, H
AU  - Jaeschke H
LA  - eng
GR  - ES-06091/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antibodies)
RN  - 0 (Endotoxins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - 7535-00-4 (Galactosamine)
RN  - WHI7HQ7H85 (Uridine)
SB  - IM
CIN - Hepatology. 1998 Sep;28(3):865-7. PMID: 9731584
MH  - Animals
MH  - Antibodies/toxicity
MH  - *Apoptosis
MH  - Cell Movement
MH  - Endothelium, Vascular/*cytology
MH  - Endotoxins/*toxicity
MH  - Galactosamine/toxicity
MH  - Liver/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Neutrophils/*physiology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Uridine/pharmacology
MH  - fas Receptor/*physiology
EDAT- 1998/09/10 00:00
MHDA- 1998/09/10 00:01
CRDT- 1998/09/10 00:00
PHST- 1998/09/10 00:00 [pubmed]
PHST- 1998/09/10 00:01 [medline]
PHST- 1998/09/10 00:00 [entrez]
AID - S0270913998003723 [pii]
AID - 10.1002/hep.510280324 [doi]
PST - ppublish
SO  - Hepatology. 1998 Sep;28(3):761-7. doi: 10.1002/hep.510280324.