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Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1579-1585
Receptor Clearance Obscures the Magnitude of Granulocyte-Macrophage
Colony-Stimulating Factor Responses in Mice to Endotoxin or Local
Infections
Donald Metcalf,
Nicos A. Nicola,
Sandra Mifsud, and
Ladina Di Rago
From the Division of Cancer and Haematology, The Walter and Eliza
Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria,
Australia.
Marrow cells from mice lacking high-affinity receptors for
granulocyte-macrophage colony-stimulating factor (GM-CSF;
c / mice) were shown to bind and internalize much
less GM-CSF than cells from normal ( c+/+) mice.
c / mice were used to determine the effect of
negligible receptor-mediated clearance on detectible GM-CSF responses
to the intravenous injection of endotoxin or the intraperitoneal
injection of casein plus microorganisms. Unlike the minor serum GM-CSF
responses to endotoxin seen in c+/+ mice, serum
GM-CSF levels rose 30-fold to 9 ng/mL in c / mice
even though loss of GM-CSF in the urine was greater than in
c+/+ mice. Organs from c / and
c+/+ mice had a similar capacity to produce GM-CSF
in vitro, as did peritoneal cells from both types of mice when
challenged in vitro by casein. However, when casein was injected
intraperitoneally, c / mice developed higher and
more sustained levels of GM-CSF than did c+/+ mice.
The data indicated that receptor-dependent removal of GM-CSF masks the
magnitude of GM-CSF responses to endotoxin and local infections.
Because of this phenomenon, serum GM-CSF concentrations can be a
misleading index of the occurrence or nonoccurrence of GM-CSF responses
to infections.

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