In vivo modulation of myelopoiesis by XXXX . IV. @entity1421 induction of myelopoietic inhibitory activity.

@entity558 @entity19 @entity1421 @entity3323 @entity5014
@entity558 ( @entity558 ) prepared from bone marrow (BM) or spleen (SPL) cells from @entity19 injected with @entity1421 in doses ranging from 0.0001 to 10 micrograms was found to contain an activity inhibitory to the proliferation of granulocyte-monocyte progenitor cells (CFU-GM). This activity was found in medium conditioned for 24 to 48 h, but was not present in medium conditioned for longer time intervals. BM cells from @entity1421 -treated @entity19 incubated over a concentration range of 0.1 to 1.0 x 10(6) cells/ml and SPL cells over a range of 1.0 to 10 x 10(6) cells/ml produced @entity558 with equivalent degrees of inhibition for CFU-GM proliferation. Titration of this activity revealed a significant inhibitory effect still present at a 1/256 dilution. Inhibitory activity was similar whether or not @entity558 was prepared in the presence or absence of FCS. Inhibition of CFU-GM development was approximately equal in the presence of either PWM SPL @entity558 or L cell @entity558 as sources of CSF activity. Morphologic analysis of CFU-GM revealed an equivalent inhibition of monocyte, monocyte-neutrophil, and neutrophil CFU-GM by the @entity1421 -stimulated inhibitory activity. Equivalent picogram amounts of @entity5014 were measured in @entity558 derived from BM or SPL cells from either control or @entity1421 -treated @entity19 , indicating a low probability that injected @entity1421 was carried over in the @entity558 and contributed to CFU-GM inhibition. Protease digestion of BM or SPL cell @entity558 from @entity1421 -treated @entity19 revealed a loss of inhibitory activity after trypsin, chymotrypsin, pronase, and neuraminidase treatment. Inhibitory activity was also ablated by heat treatment at 56 degrees C for 30 min and 100 degrees C for 5 min. @entity3323 -agarose gel filtration of BM @entity558 revealed an active inhibitory fraction in the Mr range of 5.5 to 8.0 kDa. The results of the present study suggest that one of the mechanisms by which @entity1421 exerts its in vivo myelopoietic inhibitory action may be by stimulating the production of an inhibitory factor or factors from BM and SPL cells.
