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.
Division of Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
D
D
Metcalf
N A
NA
Nicola
S
S
Mifsud
L
L
Di Rago
D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D002364:Caseins / Q000008:administration & dosage; D002614:Chelating Agents / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism*
D002364:Caseins; D002614:Chelating Agents; D008070:Lipopolysaccharides; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor