Cytokine production by primary bone marrow megakaryocytes
S Jiang, JD Levine, Y Fu, B Deng, R London, JE Groopman and H Avraham
Division of Hematology/Oncology, New England Deaconess Hospital, Boston, MA
02215.
Primary human bone marrow megakaryocytes were studied for their ability to
express and release cytokines potentially relevant to their proliferation
and/or differentiation. The purity of the bone marrow megakaryocytes was
assessed by morphologic and immunocytochemical criteria. Unstimulated
marrow megakaryocytes constitutively expressed genes for interleukin-1 beta
(IL-1 beta), IL-6, granulocyte-macrophage colony-stimulating factor
(GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), by the polymerase
chain reaction (PCR) and Northern blot analysis. At the protein level,
megakaryocytes secreted significant amounts of IL-1 beta (53.6 +/- 3.6
pg/mL), IL-6 (57.6 +/- 15.6 pg/mL), and GM-CSF (24 +/- 4 pg/mL) but not
TNF-alpha. Exposure of human marrow megakaryocytes to IL-1 beta increased
the levels of IL-6 (87.3 +/- 2.3 pg/mL) detected in the culture
supernatants. Transforming growth factor- beta was also able to stimulate
IL-6, IL-1 beta, and GM-CSF secretion, but was less potent than stimulation
with phorbol-12-myristate-13- acetate (PMA). The secreted cytokines acted
additively to maintain and increase the number of colony-forming
unit-megakaryocytes colonies (approximately 35%). These studies demonstrate
the production of multiple cytokines by isolated human bone marrow
megakaryocytes constitutively or stimulated in vitro. The capacity of human
megakaryocytes to synthesize several cytokines known to modulate
hematopoietic cells supports the concept that there may be an autocrine
mechanism operative in the regulation of megakaryocytopoiesis.
Volume 84,
Issue 12,
pp. 4151-4156,
12/15/1994
Copyright © 1994 by The American Society of Hematology
