Synergism between interleukin-6 and interleukin-3 in supporting proliferation of human hematopoietic stem cells: comparison with interleukin-1 alpha.
Currently available evidence suggests that in the steady state, the majority of hematopoietic stem cells are dormant in cell cycle and reside in the so-called G0 period. Studies in our laboratory indicated that once a stem cell leaves G0, its subsequent proliferation requires the presence of interleukin-3 (IL-3). Recently it was reported that interleukin-1 (IL-1) may stimulate stem cells to become sensitive to IL-3. In a separate study, we observed that interleukin-6 (IL-6, also known as B cell stimulatory factor-2/interferon beta 2) possesses synergism with IL-3, shortening the G0 period of murine hematopoietic stem cells. We report here that human IL-6 and IL-3 act synergistically in support of the proliferation of progenitors for human blast cell colonies and that IL-1 alpha reveals no synergism with IL-3 when tested against purified human marrow progenitors. Panned My-10+ human marrow cells were plated in culture and on day 14 of incubation, either IL-3, IL-6, IL-1 alpha or a combination of these factors was added to the cultures. Blast cell colony formation was analyzed daily between days 18 and 32 of culture. IL-6 or IL-1 alpha alone failed to support blast cell colony formation. In the presence of IL-3 alone, blast cell colonies continued to emerge between days 21 and 27. When a combination of IL-3 and IL-6 was added, blast cell colonies developed earlier than in cultures with IL-3 alone and twice as many blast cell colonies were identified. IL-1 alpha failed to augment IL-3-dependent blast cell colony formation. Replating studies of the individual blast cell colonies revealed various types of single as well as multilineage colonies. These observations suggest that IL-6 shortens the G0 period of human hematopoietic stem cells and that the reported synergistic activities of IL-1 on primitive hematopoietic cells may be indirect.
Leary
A G
AG
VA Medical Center, Charleston, SC.
Ikebuchi
K
K
Hirai
Y
Y
Wong
G G
GG
Yang
Y C
YC
Clark
S C
SC
Ogawa
M
M
D002478:Cells, Cultured; D004357:Drug Synergism; D004921:Erythropoietin; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology*; D011994:Recombinant Proteins
D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D007378:Interleukins; D011994:Recombinant Proteins; D004921:Erythropoietin