Effects of L-leucyl-L-leucine methyl ester on human marrow and protection of progenitor cells by IL-1.
In murine models, L-leucyl-L-leucine methyl ester (LLME) is effective as an ex vivo purging agent for the prevention of graft-versus-host disease. However, reduction of progenitor cells by LLME raises concerns about the engraftment potential of LLME-treated marrow. Therefore, the effects of LLME on human marrow were investigated. Concentrations of LLME from 0.005 mM to 5 mM were used to examine the effects of LLME on marrow cells. Concentrations of LLME less than or equal to 0.05 mM had no effect on recovery of nucleated marrow cells, mononuclear cells (MNC), myeloid cells or monocytes. At 0.5 mM, nucleated marrow cell recovery was 25%, and MNC recovery was 93%. As determined by cytochemical stains, 0.5 mM LLME eliminated myeloid cells and monocytes. At 0.005 mM, LLME had little effect on marrow progenitor cells; progenitor cell recovery with 0.05 mM LLME was 35% for granulocyte-macrophage colony forming units (CFU-GM) and 23% for erythroid burst forming units (BFU-E) (p less than 0.05 compared to 0.005 mM). At higher LLME concentrations, recoveries of both CFU-GM and BFU-E were less than 1%. To determine if earlier hematopoietic cells remained after treatment with LLME, progenitor cell experiments were repeated with 0.5 mM LLME using recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) or recombinant human interleukin 3 (rhIL-3) plus or minus recombinant human mast cell growth factor (rhMGF) as sources of colony-stimulating activity. In this system, both IL-3 and GM-CSF induced rare progenitor cells (less than 6/5 x 10(4) cells plated).(ABSTRACT TRUNCATED AT 250 WORDS)
Rosenfeld
C S
CS
West Penn Hospital, Western Pennsylvania Cancer Institute, Pittsburgh 15224.
D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D007377:Interleukin-3 / Q000502:physiology; D013234:Stem Cells / Q000737:chemistry / Q000187:drug effects*
D004151:Dipeptides; D007375:Interleukin-1; D007377:Interleukin-3; C045139:leucyl-leucine-methyl ester