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BR Blazar, SL Aukerman and DA Vallera
Department of Pediatrics, University of Minnesota Hospital and Clinic,
Minneapolis.
Recombinant macrophage colony-stimulating factor (rM-CSF), which reacts
exclusively with cells of monocyte lineage, was evaluated in the murine
bone marrow (BM) transplant setting for in vivo effects on recipient
survival, hematologic recovery, and engraftment. Two types of fully
allogeneic donors were selected based on the expression (BALB/c), or lack
of expression (DBA/1), of hybrid hematopoietic histocompatibility (Hh1)
antigens. These antigens are established targets for monocyte and/or
natural killer (NK) cell-mediated graft rejection. Irradiated C57BL/6 mice
were used as recipients for all experiments. Recipients of T-cell-depleted
(TCD) BALB/c BM and a 14-day continuous subcutaneous infusion of 16.8
micrograms/d rM-CSF (n = 30) showed a significant decrease in donor cell
engraftment as compared with recipients of donor BM administered pumps
delivering saline. These mice administered rM-CSF also displayed
significantly reduced levels of circulating leukocytes (predominantly
lymphocytes) on day 14 posttransplant (compared with saline controls).
Neither engraftment effects nor leukocyte effects were observed when
C57BL/6 recipients were administered Hh1 nonexpressing TCD DBA/1 BM cells
(n = 30), suggesting that the monocyte/macrophage population is important
in long-term alloengraftment in certain donor-recipient strain combinations
in which donor Hh1 antigens can serve as target antigens for host effector
cells, but are not important in strain combinations in which they are not
recognized. Circulating tumor necrosis factor alpha (TNF alpha) levels
measured at two time periods during rM-CSF infusion were not elevated.
Thus, the reduction in alloengraftment is not likely to be directly related
to TNF alpha. However, in vivo elimination of NK cells in the BALB/c into
C57BL/6 model prevented the impairment of engraftment mediated by rM-CSF.
Thus, rM-CSF-mediated inhibition of alloengraftment is contingent on the
presence of host NK cells with antidonor reactivity. Survival was
unaffected when rM-CSF was administered in either allogeneic BM transplant
model, but was significantly reduced when rM-CSF was administered to
C57BL/6 recipients of syngeneic BM transplants. These data are the first
analyzing the effects of rM-CSF in murine allogeneic BM transplantation and
extend our previous studies using the BALB/c into C57BL/6 model in which in
vivo infusions of recombinant granulocyte-macrophage CSF, but not
recombinant granulocyte-CSF, lead to decreases in alloengraftment. These
data show that rM-CSF-induced stimulation of monocytes may increase BM
graft rejection in instances in which NK cells are involved in the
rejection process. These data may have future clinical implications for the
use of rM-CSF in allogeneic BM transplantation.
This article has been cited by other articles:
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
