Fibroblast growth factor 9 (FGF-9), a novel member of the FGF family,
was found to have thrombopoietic activity in vitro and in vivo. In an
in vitro megakaryocyte colony-stimulating factor assay, anti-mouse int
erleukin-6 (IL-6) monoclonal antibody neutralized FGF-9 activity. This
suggests that the activity may be exerted via IL-6 induction. BALB/c
mice that received subcutaneous FGF-9 injections of 4 to 100 mu g/day
for 2 weeks showed a dose-dependent transient increase in peripheral p
latelet counts 10 to 12 days after the first treatment. Histologic stu
dies showed a marked increase in megakaryocytes in the bone marrow and
extramedullary hematopoiesis in the spleen and the liver. Examination
of changes in the DNA content of bone marrow megakaryocytes revealed
that the ploidy distribution underwent a marked shift 3 days after FGF
-9 injection, with a large increase in the 2N megakaryocyte population
. The major modal ploidy shifted from the normal 16N to 2N. The number
of megakaryocyte progenitor cells in FGF-9 treated mice increased up
to 1.5-fold in the bone marrow and 10-fold in the spleen on day 6. The
se results indicate that FGF-9 acts on the in vivo proliferation of me
gakaryocytes.