Receptor clearance obscures the magnitude of granulocyte-macrophage colony-stimulating factor responses in mice to endotoxin or local infections
- Author(s)
- Metcalf, D; Nicola, NA; Mifsud, S; Di Rago, L;
- Details
- Publication Year 1999-03-01,Volume 93,Issue #5,Page 1579-1585
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- Abstract
- 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. (C) 1999 by The American Society of Hematology.
- Publisher
- AMER SOC HEMATOLOGY
- Keywords
- CSF TRANSGENIC MICE; GM-CSF; SERUM; GRANULOPOIESIS; HEMATOPOIESIS; NEUTROPENIA; BIOASSAYS; LACKING; DEVELOP
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Creation Date: 1999-03-01 12:00:00