Km. Howard et al., CELL-SPECIFIC REGULATION OF EXPRESSION OF PLASMA-TYPE PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE IN THE LIVER, The Journal of biological chemistry, 272(44), 1997, pp. 27543-27548
Platelet-activating factor (PAF) is a potent proinflammatory phospholi
pid mediator that causes hypotension, increases vascular permeability,
and has been implicated in anaphylaxis, septic shock and several othe
r inflammatory responses. PAF is hydrolyzed and inactivated by the enz
yme PAF-acetylhydrolase. In the intact rat, a mesenteric vein infusion
of lipopolysaccharide (LPS) served as an acute, liver-focused model o
f endotoxemia, Plasma PAF-acetylhydrolase activity increased 2-fold by
24 h following LPS administration. Ribonuclease protection experiment
s demonstrated very low levels of plasma-type PAF-acetylhydrolase mRNA
transcripts in the livers of saline-infused rats; however, 24 h follo
wing LPS exposure, a 20-fold induction of PAF-acetylhydrolase mRNA was
detected. In cells isolated from endotoxin-exposed rat Livers, Northe
rn blot analyses demonstrated that Kupffer cells but not hepatocytes o
r endothelial cells were responsible for the increased PAF-acetylhydro
lase mRNA levels, In Kupffer cells, plasma-type PAF-acetylhydrolase mR
NA was induced by 12 h, peaked at 24 h, and remained substantially ele
vated at 48 h, Induction of neutropenia prior to LPS administration ha
d no effect on the increase in PAF-acetylhydrolase mRNA seen at 24 h.
Although freshly isolated Kupffer cells contain barely detectable leve
ls of plasma-type PAF-acetylhydrolase mRNA when Kupffer cells were est
ablished in culture, PAF-acetylhydrolase expression became constitutiv
ely activated concomitant with cell adherence to the culture plates, A
lterations in plasma-type PAF-acetylhydrolase expression may constitut
e an important mechanism for elevating plasma PAF-acetylhydrolase leve
ls and an important component in minimizing PAF-mediated pathophysiolo
gy in livers exposed to endotoxemia.