In vivo interleukin-1 (IL-1) administration indirectly promotes type II
IL-1 receptor expression on hematopoietic bone marrow cells: novel
mechanism for the hematopoietic effects of IL-1
CM Dubois, FW Ruscetti, JR Keller, JJ Oppenheim, K Hestdal, R Chizzonite and R Neta
Program Resources, Inc/DynCorp, National Cancer Institute-Frederick Cancer
Research and Development Center, MD.
Interleukin-1 (IL-1) has profound stimulatory effects on hematopoiesis but
the mechanism(s) of action remain unknown. The direct action of IL- 1 on
hematopoietic progenitor cells requires the presence of a specific IL-1
receptor (IL-1R). In this report, we tested the effect of in vivo IL-1
treatment on the expression of IL-1R on bone marrow (BM) cells. Injection
of mice with IL-1 results in a marked upregulation of IL-1R on
light-density BM cells as on a subpopulation enriched for myeloid
precursors. Pretreatment of mice with anti-type I IL-1R antibody (35F5),
which has been shown to prevent the radioprotective effect of IL-1, also
blocked IL-1-induced IL-1R expression on BM cells. This antibody did not
directly bind and block IL-1 binding to the type II IL- 1R expressed on
hematopoietic cells, suggesting that IL-1R upregulation by IL-1 is
indirect. It is therefore possible that IL-1 acts on type I
IL-1R-expressing accessory cells such as stromal cells or T cells to induce
production of hematopoietic growth factors (HGFs). In support of this,
granulocyte colony-stimulating factor administration can induce the
increase of IL-1R on BM cells. Thus, the increased expression of IL- 1R on
hematopoietic BM cells by IL-1 is indirect, probably mediated in part
through endogenous HGF production. These results also suggest that the
restorative hematopoietic effect of IL-1 occurs through both indirect and
direct mechanisms.
Volume 78,
Issue 11,
pp. 2841-2847,
12/01/1991
Copyright © 1991 by The American Society of Hematology
