The human promyelocytic
leukemia cell line HL-60 and monoblastic
leukemia cell line U937 undergo differentiation when induced by lymphokine and
cytokine preparations. Growth inhibition, acquisition of
immunoglobulin Fc receptors, increased expression of monocyte-related
surface antigens, and an increase in lysosomal
enzyme contents accompany maturation induced by
gamma-interferon and other
cytokine factors tested. Additionally, increased receptors for chemotactic
peptide (fMLPR), increased
hydrogen peroxide release in response to
phorbol myristic
acetate stimulation, and the release of
prostaglandins (PGE2 and 6-keto-PGF1a) follow exposure to lymphokine and cell line sources of myeloid colony-stimulating activity (CSA).
Gamma-Interferon (gamma-IFN) induced fMLPR in HL-60 (only at 1000 units/ml) but not in U937. Additionally, gamma-IFN did not induce
prostaglandin release in either cell line. These myeloid colony-stimulating activity-associated differentiation-inducing factors were obtained from the human
hepatoma++ cell line SK-Hep and bladder
carcinoma cell line 5637, which were free of
interferon activity. The 2-day
phytohemagglutinin-induced lymphokine contained no detectable CSA and was a good source of differentiation activity. A simple, rapid assay for a new human CSA with pluripotent hematopoietic stimulating activity (pluripoietin) is described based on stimulation of [3H]
glucosamine incorporation. Cell line
conditioned media containing pluripoietin, purified pluripoietin, and gamma-IFN are active in this assay. These
myeloid leukemia cell line differentiation factors are thus different from
interferon and conventional CSA. These results suggest that endogenous human
cytokines may have a role in the differentiation of leukemic as well as normal myeloid cells.