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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; beta c-/- mice) were shown to bind and internalize much less GM-CSF than cells from normal (beta c+/+) mice. beta 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 beta c+/+ mice, serum GM-CSF levels rose 30-fold to 9 ng/mL in beta c-/- mice even though loss of GM-CSF in the urine was greater than in beta c+/+ mice. Organs from beta c-/- and beta 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, beta c-/- mice developed higher and more sustained levels of GM-CSF than did beta 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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