Liver‐associated macrophage precursor cells proliferate under impairment of regular hemopoiesis

Decker, Thomas; Lohmann‐Matthes, Marie‐Luise; Baccarini, Manuela

doi:10.1002/eji.1830180507

Cited by 26 publications

(26 citation statements)

References 41 publications

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“…We argue that demonstration of these progenitors in the presence of other lineages in peripheral blood mononuclear cells (PBMCs) would provide strong evidence for engraftment of stem cells in organ recipients given adjunct bone marrow (BM) infusion (21). Added to previous observations in rodents (22)(23)(24)(25)(26), such findings would explain the long-term perpetuation of multi-lineage donor cell chimerism in all successful organ allograft recipients decades after transplantation (3,4).Here, we present evidence that chimerism in BM-augmented organ transplant human recipients is indeed multilineage. Culture of their peripheral blood in recombinant human granulocytemacrophage colony-stimulating factor (rhGM-CSF)-and interleukin 4 (rhIL-4)-enriched medium resulted in propagation of progenitors of DCs, which were confirmed to be those of donor origin.…”

supporting

confidence: 65%

Section: Introductionmentioning

confidence: 83%

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Evidence for the Presence of Multilineage Chimerism and Progenitors of Donor Dendritic Cells in the Peripheral Blood of Bone Marrow-Augmented Organ Transplant Recipients1

Rugeles

Aı̈touche²,

Zeevi³

et al. 1997

Transplantation

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We have postulated that the donor leukocyte microchimerism plays a seminal role in the acceptance of allografts by inducing and perpetuating variable degree of donor-specific nonreactivity in longsurviving organ recipients. Limited information is available, however, concerning the phenotype and function of these chimeric cells in humans. The unequivocal presence of donor dendritic cells (DCs), a prominent lineage in the microchimerism observed in rodents and clinical organ recipients, was difficult to demonstrate in bone marrow (BM)-augmented organ transplant recipients. This enigma was resolved by the recent description of a method for propagating circulating human DCs from their progenitors by culture in a medium enriched with granulocyte-macrophage colony-stimulating factor and interleukin 4, a condition known to inhibit outgrowth of monocytes, thus providing a selective growth advantage to committed progenitors of the myeloid lineage. Cells from BM-augmented organ recipients and normal control subjects harvested from 12-to 14-day cultures exhibited dendritic morphology and potent allostimulatory capacity. Using appropriate primers, the presence of donor DNA was verified by polymerase chain reaction within the lineage null /class II bright sorted DC. Phenotypic analysis of cultured DCs from BM-augmented patients, unlike that of controls, exhibited a marked down-regulation of B7-1 (CD80) while retaining normal levels of expression of B7-2 (CD86) cell surface molecules. The presence of donor DNA was also confirmed by polymerase chain reaction in individually sorted lineage + (T, B, and NK) cells and macrophages, suggesting that the chimerism in BM-augmented patients is multilineage. The presence of progenitors of donor DCs in the peripheral blood of BM-augmented patients further substantiates the already convincing evidence of stem cell engraftment. The diffuse migration of passenger leukocytes from transplanted organs into the recipient has been proposed as the first step toward allograft acceptance and the induction of variable degrees of donor-specific tolerance (1-4). In this paradigm, acceptance of various organs hinges on the quantity and quality of tolerogenic resident migratory cells with a critical role for cells of the dendritic leukocyte lineage (5-11) first characterized by Steinman and Cohn (12,13). Although dendritic cells (DCs * ) and their progenitors have been isolated from various mouse (14-18) and rat (19) tissues, such studies were not possible in humans until Romani et al. (20) described a modified culture technique for propagation of DCs from their progenitors in human blood. We argue that demonstration of these progenitors in the presence of other lineages in peripheral blood mononuclear cells (PBMCs) would provide strong evidence for engraftment of stem cells in organ recipients given adjunct bone marrow (BM) infusion (21). Added to previous observations in rodents (22)(23)(24)(25)(26), such findings would explain the long-term perpetuation of multi-lineage donor cell chimerism i...

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supporting

confidence: 65%

Section: Introductionmentioning

confidence: 83%

Evidence for the Presence of Multilineage Chimerism and Progenitors of Donor Dendritic Cells in the Peripheral Blood of Bone Marrow-Augmented Organ Transplant Recipients1

Rugeles

Aı̈touche²,

Zeevi³

et al. 1997

Transplantation

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“…The mechanism of this cytotoxic action of the cytokine is not fully understood, but the involvement of a cytolytic proteinase activated in stimulated macrophages is widely assumed [36]. A cell-associated form of TNF serves in the killing of tumor cells by activated cytotoxic murine macrophages [168]. In fibroblasts, TNF profoundly affects gene regulation stimulating the ,fos and myc genes [174].…”

Section: Tumor Necrosisjuctor a (Cuchectin)mentioning

confidence: 99%

Biologically active products of stimulated liver macrophages (Kupffer cells)

Decker

1990

European Journal of Biochemistry

845

456

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“…A quantitative assay of cell death was performed by flow cytometry, measuring the percentage of PI-incorporating cells, as described above, and by measuring lactate dehydrogenase (LDH) leakage into the medium from damaged cells [20]. To measure LDH release, thymocytes (1 ml\well) were incubated for 24 h, the cells were then collected by centrifugation and the fraction of LDH activity released from dead cells was measured spectrophotometrically in the supernatant.…”

Section: Cell Deathmentioning

confidence: 99%

ATP depletion inhibits glucocorticoid-induced thymocyte apoptosis

Stefanelli

Bonavita

Stanic

et al. 1997

Biochemical Journal

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In quiescent thymocytes, mitochondrial de-energization was not correlated to apoptotic death. In fact, thymocytes treated with oligomycin, a highly specific inhibitor of ATP synthase, alone or with atractyloside to block ATP translocation from the cytoplasm, were alive, even if their mitochondria were depolarized, as revealed by flow cytometry after Rhodamine 123 staining. Furthermore, oligomycin was a powerful inhibitor of apoptosis induced in rat thymocytes by dexamethasone and, to a lesser extent, by the calcium ionophore A23187 and etoposide, but was without effect when apoptosis was induced by staurosporine, and increased cell death in mitogen-treated thymocytes. The inhibition of apoptosis was confirmed by morphological criteria, inhibition of inter-nucleosomal DNA fragmentation and inhibition of the loss of membrane integrity. The anti-apoptotic effect of oligomycin in cells treated with A23187 or etoposide was correlated to the inhibition of protein synthesis, while inhibition of apoptosis induced by dexamethasone, already evident at an oligomycin concentration of 10 ng\ml, was instead strictly cor-

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Liver‐associated macrophage precursor cells proliferate under impairment of regular hemopoiesis

Cited by 26 publications

References 41 publications

Evidence for the Presence of Multilineage Chimerism and Progenitors of Donor Dendritic Cells in the Peripheral Blood of Bone Marrow-Augmented Organ Transplant Recipients1

Evidence for the Presence of Multilineage Chimerism and Progenitors of Donor Dendritic Cells in the Peripheral Blood of Bone Marrow-Augmented Organ Transplant Recipients1

Biologically active products of stimulated liver macrophages (Kupffer cells)

ATP depletion inhibits glucocorticoid-induced thymocyte apoptosis

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