Neutrophil margination and extravasation in sinusoids and venules
of the liver during endotoxin-induced injury.
Chosay, John G., Naeem A. Essani, Colin J. Dunn, and Hartmut Jaeschke.
Cell Biology and Inflammation Research and Cardiovascular
Pharmacology, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan
49007
APStracts 3:0270G, 1996.
Neutrophils contribute to liver damage during endotoxin shock. The
objective of this investigation was to document where neutrophil
localize in the hepatic vasculature and if they migrate out of
sinusoids or postsinusoidal venules using a well-characterized model
of galactosamine/endotoxin shock and immunostaining for neutrophil
-associated MRP8/MRP14 S100 calcium binding proteins. Treatment of
C3Heb/FeJ mice with 100 [mu]g/kg Salmonella abortus equi endotoxin
alone or in combination with 700 mg/kg galactosamine induced a time
-dependent increase of neutrophil margination in sinusoids and
postsinusoidal venules at 4 h. The number of venular neutrophils
decreased in both groups at later time points without evidence for
transmigration. Extravasation of neutrophils was only observed from
sinusoids in galactosamine/endotoxin-treated animals between 4-7h,
which correlated with parenchymal cell injury. After endotoxin alone,
large numbers of neutrophils remained sequestered in sinusoids
without injury. These data suggest that neutrophils cause
hepatocellular injury during endotoxemia after extravasation and are
less likely to cause damage when sequestered in the vasculature. In
the liver, neutrophils migrate out of sinusoids and not out of
postsinusoidal venules.
Received 31 May 1996; accepted in final form 25 November 1996.
APS Manuscript Number G218-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996