Human thymic epithelial cells produce granulocyte and macrophage colony-stimulating factors.
The development of culture conditions for growing normal human thymic epithelial (TE) cells free from contamination with other stromal cells has allowed us to identify and characterize TE cell-derived cytokines. In this study, we report that cultured human TE cells produced CSF that supported the growth of clonal hematopoietic progenitor cells in the light density fraction of human bone marrow cells. Thymic epithelial supernatants (TES) induced growth of granulocyte/macrophage colonies (CFU-GM), mixed granulocyte/erythrocyte/monocyte/megakaryocyte colonies (CFU-GEMM), and early burst-forming unit erythroid colonies (BFU-E). In addition, TES induced differentiation of the promyelocyte leukemic cell line HL-60 and stimulated growth of both granulocyte (CFU-G) and monocyte (CFU-M) colonies from murine bone marrow cells. Using anion exchange column chromatography, pluripotent CSF activities in TES were separated and shown to be distinct from an IL-1-like cytokine that has been shown as a TE cell-derived cytokine (TE-IL-1). Colony-stimulating activity supporting the growth of bone marrow CFU-GEMM, BFU-E, and CFU-GM co-eluted at 150 to 180 mM NaCl. A separate peak of CFU-GM-stimulating activity eluted early in the gradient at 20 mM NaCl. In Northern blot analysis of enriched RNA, synthetic oligonucleotide probes complementary to human G-CSF and M-CSF coding sequence each hybridized with a single RNA species of 1.7 and 4.4 kb, respectively. These data suggest that normal human TE cells synthesize G-CSF and M-CSF that promote differentiation of non-lymphoid hematopoietic cell precursors.
Le
P T
PT
Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
Kurtzberg
J
J
Brandt
S J
SJ
Niedel
J E
JE
Haynes
B F
BF
Singer
K H
KH
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002474:Cell-Free System; D002648:Child; D002852:Chromatography, Ion Exchange; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D016298:Hematopoietic Cell Growth Factors; D006801:Humans; D007118:Immunoassay; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000302:isolation & purification; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D016179:Granulocyte Colony-Stimulating Factor; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor