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-macr ophage colony-stimulating factor (GM-CSF; beta c(-/-) mice) were shown to b ind and internalize much less GM-CSF than cells from normal (beta c(+/+)) m ice, beta c(-/-) mice were used to determine the effect of negligible recep tor-mediated clearance on detectible GM-CSF responses to the intravenous in jection of endotoxin or the intraperitoneal injection of casein plus microo rganisms. 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(-/-) mi ce 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 t o 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 intra peritoneally, beta c(-/-) mice developed higher and more sustained levels o f GM-CSF than did beta c(+/+) mice. The data indicated that receptor-depend ent removal of GM-CSF masks the magnitude of GM-CSF responses to endotoxin and local infections. Because of this phenomenon, serum GM-CSF concentratio ns can be a misleading index of the occurrence or nonoccurrence of GM-CSF r esponses to infections. (C) 1999 by The American Society of Hematology.