Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Umbilical cord blood (CB) transplantations are associated with a lower risk of severe graft-versus-host disease (GVHD) compared to BMT. GVHD is an immune reaction that involves interaction between cell surface molecules resulting in cell activation and release of many cytokines. Monocytes are known to be an important source of cell adhesion (CAM) and co-stimulatory molecules which play a crucial role in the efficient activation of T and B cells. We analyzed the phenotype of CB monocytes in the presence or absence of an inflammatory signal (rIFN-gamma) and compared them to adult blood (AB); the expression of HLA-DR and 17 different markers (CD11a, CD11b, CD11c, CD18, CD29, CD40, CD44, CD49a, CD49d, CD49e, CD49f, CD54, CD58, CD62L, CD80, CD86 and CD102) was measured by flow cytometry. Statistical analysis showed that, compared to AB, CB monocytes did not express CD11b, CD11c, CD49d and after stimulation with rIFNgamma, they lost the expression of CD58 and CD102, whereas CD80 and CD86 expression was induced. The analysis of fluorescence intensity (MFI) revealed that CB monocytes expressed some CAM (CD29, CD54, CD102) with a lower intensity than AB monocytes except CD44. In conclusion, absence and reduced expression of some markers argue for a different phenotypic profile of CB monocytes compared to AB monocytes, which might partly contribute to their impaired immune response and to the low incidence of GVHD observed after CB transplantations. However, CB monocytes expressed CD80 and CD86 co-stimulatory molecules, but this expression did not prove a normal co-stimulatory function.
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PMID:Expression of HLA-DR, CAM and co-stimulatory molecules on cord blood monocytes. 1116 18

Recombinant human granulocyte colony stimulating factor (rhG-CSF)-mobilized peripheral blood stem cells (PBSC) are now widely used for allogeneic PBSC transplantation (alloPBSCT). Large numbers of hematopoietic progenitor cells mobilized by rhG-CSF would be considered equivalent or better than bone marrow (BM) cells and would be used as an alternative to BM for allogeneic hematopoietic stem cell transplantation. The complications associated with the administration of rhG-CSF and apheresis in PBSC collection in formal donors are well tolerated and usually acceptable in the short term but some hazardous adverse events such as splenic rupture and cardiac arrest are reported although the incidence is very low. Protective means and stopping rules for safe donation in the collection of PBSC are established. The characteristics of PBSC were clarified; the expression of some adhesion molecules such as CD49d on CD34 positive cells of PBSC have been shown to be low compared to BM stem cells. In alloPBSCT compared with allogeneic BM transplantation (alloBMT), the incidence and frequency of graft versus host disease (GVHD) is of concern because high number of T lymphocytes are infused in alloPBSCT. The incidence and severity of acute GVHD are not increased but chronic GVHD is higher in alloPBSCT compared with alloBMT. The outcome of alloPBSCT and BMT are almost equivalent and conclusive results regarding survival are not yet available.
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PMID:Application of peripheral blood stem cells (PBSC) mobilized by recombinant human granulocyte colony stimulating factor for allogeneic PBSC transplantation and the comparison of allogeneic PBSC transplantation and bone marrow transplantation. 1212 Oct 68

The role of NK cells in allogeneic HCT has been increasingly appreciated, particularly in the GVL effect. Although FK506 has been used widely to prevent GVHD, its action was considered to be primarily through activated T cells. In this study, we provide direct evidence for the first time that human NK cells are immediate targets of FK506. Our in vivo data from patients undergoing peripheral blood stem cell transplantation or BMT showed a reduced number of NK cells with down-regulated CD25 expression in their peripheral blood compartment. Likewise, FK506 caused profound inhibition of NK cell proliferation in vitro and suppressed NK cytotoxicity and cytokine secretion in response to IL-2. These defects were accompanied by impaired cell clustering and selective down-regulation of adhesion molecules, ICAM-1, CD2, CD49d, and CD58. Furthermore, FK506 specifically inhibited expression of NKG2D, CD48, and DNAM1 receptors without affecting that of 2B4, NKp30, NKp44, and NKp46. As a result, natural cytotoxicity against K562 tumor targets was impaired, while leaving redirected ADCC via 2B4 intact. Finally, FK506-treated NK cells showed impaired IL-2R signaling and inhibition of STAT3. Collectively, these signaling impairments and selective down-regulation of NK receptors by FK506 may underlie the proliferative and functional defects of NK cells. Thus, our data provide a new insight into the mechanism of immunosuppression by FK506, which should be considered to interpret the outcome of graft transplantation.
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PMID:FK506 causes cellular and functional defects in human natural killer cells. 2067 Nov 92