Enhanced resistance of bone marrow transplanted mice to bacterial infection
induced by recombinant granulocyte-macrophage colony- stimulating factor
I Bleiberg, I Riklis and I Fabian
Department of Histology and Cell Biology, Sackler School of Medicine,
Tel-Aviv University, Ramat-Aviv, Israel.
The in vivo effect of recombinant murine granulocyte-macrophage colony
stimulating factor (rGM-CSF) on the resistance of mice to bacterial
infection and on the number and function of neutrophils was studied in
lethally irradiated mice transplanted with syngeneic bone marrow cells.
Bone marrow transplanted (BMT) mice were injected intraperitoneally with
150 ng rGM-CSF or buffer solution (diluent) twice daily for 18 consecutive
days. Total neutrophil recovery from the peripheral blood and the number of
neutrophils mobilized into the peritoneal cavity were accelerated in
rGM-CSF-treated recipients. Peritoneal neutrophils isolated from mice
treated with rGM-CSF exhibited primed superoxide generation (O2-) after in
vitro stimulation with suboptimal concentrations of phorbol myristate
acetate (PMA), as compared with control mice (treated with diluent). No
additional increase in O2- production occurred upon in vitro incubation of
these cells with rGM- CSF. The protective activity of rGM-CSF was examined
in mice injected with Salmonella typhimurium. There was a 44- and 9-fold
increase in the number of S typhimurium at 96 hours postinfection in the
spleen and liver, respectively, of control mice, as compared with
rGM-CSF-treated mice, after a single injection of the bacteria (3 X 10(7)
per mouse). All the untreated control mice died within 14 days
postinoculation (1 X 10(7) bacteria per mouse), whereas 35% of the mice
treated with rGM-CSF remained alive for more than 30 days postinfection.
These findings support the concept that increased granulopoiesis and
enhanced functional activity of phagocytic cells is induced by rGM-CSF and
is responsible for enhanced resistance of BMT mice to bacterial infection.
Volume 75,
Issue 6,
pp. 1262-1266,
03/15/1990
Copyright © 1990 by The American Society of Hematology
