P. Yusoff et al., HEMATOPOIETIC COLONY-STIMULATING FACTORS CSF-1 AND GM-CSF INCREASE PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY IN MURINE BONE-MARROW-DERIVED MACROPHAGES, Growth factors, 10(3), 1994, pp. 181-192
The activity of phosphatidylinositol (PI) 3-kinase was examined in mur
ine bone marrow-derived macrophages (BMM) stimulated with the haematop
oietic growth factors colony stimulating factor-1 (CSF-1) and granuloc
yte/macrophage-CSF (GM-CSF). PI 3-kinase was immunoprecipitated from c
ell lysates using anti-phosphotyrosine antibody or an antibody directe
d against the 85K subunit of PI S-kinase, and the activity assayed by
the phosphorylation of PI in the presence of [gamma(32)P]-ATP. The res
ults demonstrate that CSF-1 increases the activity of PI 3-kinase, as
compared to the non-stimulated control, in murine macrophages. Maximum
activity was seen after 10 min of stimulation with CSF-1 at 3000-5000
U/ml. The dose-response of CSF-1 is consistent with other biochemical
effects of CSF-1 seen in the BMM. GM-CSF also stimulated PI 3-kinase
activity although to a lesser extent than CSF-1, correlating well with
their degree of mitogenic activity on the BMM. Non-mitogenic macropha
ge activating agents, such as the phorbol myristate acetate, lipopolys
accharide, concanavalin A and formyl-methionyl-leucyl-phenylalanine, d
id not significantly increase the PI 3-kinase activity. Furthermore, C
SF-1 failed to stimulate PI 3-kinase activity in resident peritoneal m
acrophages, a population of macrophages with poor proliferative capaci
ty. These results suggest that the PI 3-kinase activity may be involve
d in the haemopoietic growth factor signalling pathways regulating mac
rophage growth.