Y. Zhan et C. Cheers, Haemopoiesis in mice genetically lacking granulocyte-macrophage colony stimulating factor during chronic infection with Mycobacterium avium, IMM CELL B, 78(2), 2000, pp. 118-123
In order to test the role of granulocyte-macrophage colony stimulating fact
or (GM-CSF) in haemopoiesis during chronic infection, mice with a targeted
disruption of the gene fur GM-CSF were infected intraperitoneally with the
facultative intracellular pathogen, Mycobacterium avium. The bacteria sprea
d to lungs, liver and spleen and persisted for more than 10 weeks at levels
between 10(5) and 10(6) CFU. Bacterial numbers did not differ significantl
y between infected GM-CSF-/- and wild-type mice, making this an excellent m
odel in which to study the effects of GM-CSF deficiency on haemopoietic cel
ls without complications of interpretation relating to differences in bacte
rial load. Haemopoietic colony forming cells (CFC) in the bone marrow of GM
-CSF-/- mice before infection were not different from wild-type. However, w
hereas CFC in wild-type mice increased 1.5-fold with infection, GM-CSF-/- m
ice were unable to increase their CFC and numbers were significantly lower
than in infected wild-type mice. Cells attracted to the peritoneal cavity o
f the GM-CSF-/- mice Following i.p, injection of bacteria were notably lack
ing in the large, granular macrophages of activated appearance, which were
a feature in wild-type mice. Nitric oxide production by peritoneal cells fr
om GM-CSF-/- mice was deficient. Thus, GM-CSF is not critical for haemopoie
sis during chronic infection, but in its absence the mice are unable to inc
rease their output of haemopoietic cells and there are deficiencies in macr
ophage activation.