Kupffer Cells and PMNs as Cellular Sources That Contribute to Organ Damage During Endotoxin-Enhanced Hepatic IschemiaReferfusion Injury
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Authors
Lee, Sung-Hoon
Issue Date
1994
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Periods of hepatic ischemia (I) followed by reperfusion (RP) have been
demonstrated to produce severe injury which can act as a priming event when
combined with a secondary insult such as sepsis, to potentiate more severe injury
in the host and lead to a multiple organ failure. To better understand the
mechanisms involved in the process and to identify possible cellular sources for
reactive oxygen, a series of three related investigations were performed: l) male
Fisher rats were exposed to 20 min liver ischemia followed by RP (3 hr) and
injection of 0.5 mg/kg Salmonella enteritidis endotoxin (ET); 2) rats were treated
as above and treated with 2 mg/kg of monoclonal antibody (WT3), which was
directed against adhesion molecule of CD18; 3) rats were treated as above and
treated with 7 mg/kg of gadolinium chloride (GdCI3), which inactivated Kupffer
cells (KCs). As indicated by an increase of plasma alanine aminotransferase
(ALT) activities from 870±122 U /L (I/RP only) to 3900±470 U /L at 4 h RP,
postischemic liver injury was potentiated by ET. KCs and polymorphonuclear
cells (PMNs) were isolated from the digested liver by centrifugal elutriation (CE).
Cells isolated from experimental rats showed more spontaneous 0 2- formation
than control cells. To clearly identify the cellular source(s) of reactive oxygen in
the experimental model, the effect of KC inhibition with GdCl3 and PMN
inactivation with WT3 was examined during the early phase of RP (3h).
Inactivation of KCs protected the liver by about 50%. In contrast, PMN inhibition
did not show any attenuation in liver injury in the early phase. In addition,
when KCs and PMNs were challenged by classical stimulators such as phorbol
ester (PMA) or opsonized zymosan (OZ), KCs and PMNs were primed for
enhanced superoxide production. The following studies suggest that KCs are
responsible for oxidant stress during the initial postischemic injury phase.
Description
iv, 34 p.
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