Receptor clearance obscures the magnitude of granulocyte-macrophage colony-stimulating factor responses in mice to endotoxin or local infections.

Marrow cells from mice lacking high-affinity receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF; betac-/- mice) were shown to bind and internalize much less GM-CSF than cells from normal (betac+/+) mice. betac-/- 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 betac+/+ mice, serum GM-CSF levels rose 30-fold to 9 ng/mL in betac-/- mice even though loss of GM-CSF in the urine was greater than in betac+/+ mice. Organs from betac-/- and betac+/+ 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, betac-/- mice developed higher and more sustained levels of GM-CSF than did betac+/+ 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.