This
factor is produced by various fibroblast cell lines, antigen-stimulated
alloreactive T-lymphocytes, mitogen-activated spleen cells,
and Krebs and Ehrlich ascites cells. The factor is produced
also by monocytes after cell activation . Human lung fibroblasts
and umbilical chord endothelial cells produce LIF constitutively.
The synthesis in mesenchymal cells of LIF can be induced
by IL1-alpha, TGF-beta , EGF , and bFGF LIF is a heavily
and variably glycosylated 58 kDa protein. with a length
of 179 amino acids. Glycosylation does not appear to be
essential for bioactivity. LIF was isolated initially as
a factor that inhibits many, but not all, myeloid leukemia
cells and induces their differentiation into macrophages.
For some myeloid leukemia cell lines such as M1 a short
pulse of LIF is sufficient to initiate irreversible differentiation.
Cultured normal human bone marrow stromal cells constitutively
express LIF message. Exposure of these cells to IL1 , TGF-beta
, and TNF-alpha (but not IFN-alpha ) increases the level
of LIF mRNA. Cultured stromal cells derived from patients
with chronic myelogenous leukemia show enhanced LIF expression.
LIF may participate, either alone or through interaction
with other cytokines , in the bone marrow microenvironment
mediated influence on both normal and malignant hematopoietic
processes. LIF has been shown to be a potent inhibitor
of endothelial cell proliferation. LIF is a factor that
inhibits adipogenesis by inhibiting the lipoprotein lipase
in adipocytes. The inhibition of this enzyme probably reduces
uptake of fatty acids by adipocytes and leads to catabolism
of lipids in fat tissue. Mice with a high blood level of
LIF suffer from weight loss and are also cachectic. In
addition one also observes an accumulation of osteoblasts
in the bone marrow and formation of new bone tissues and
calcifications in the heart and skeletal muscles. A marked
increase in the number of hematopoietic cells is found
in spleen and liver. In mice injected with LIF megakaryocyte
and platelet counts rise.
|
