Effect of pharmacological purging on natural killer cell number and activity in human bone marrow

Cardoso, Angelo A.; Fallon, Margaret; Mukherji, Bijay; Silva, Maria R.G.; Marušić, Matko; Gaffney, Judith; Ascensāo, Joāo L.

doi:10.1016/0090-1229(92)90187-s

Cited by 4 publications

(7 citation statements)

References 41 publications

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“…As we have previously shown with 4HC treatment of BM (34,35), there were no significant differences between NK and T cell numbers in the control and treated cell populations (p > 0.2 for both CD3+CD56-cells and CD3-CD56+ cells) (Fig. 1A).…”

Section: Resultssupporting

confidence: 72%

“…We previously demonstrated that ex vivo bone marrow purging with 4HC is able to destroy NK cell progenitors (34), although this lineage can fully recover in the presence of interleukin 2 (IL-2) (35). In (Costar Corp, Cambridge, MA) in 15 ml of IMDM supplemented with 10% equine serum (Hyclone Laboratories, Logan, UT), 10% fetal bovine serum (FBS) (Hyclone), 2 X 10~6 M hydrocortisone (Sigma), and 1% penicillin G sodium (10,000 U/ml)-streptomycin sulfate (10,000 mg/ml) (Gibco) for 3-4 weeks at 37°C in a 5% C02 humidified air atmosphere.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Effects of Etoposide Purging on Natural Killer Cells

Silva¹,

Ascensāo²

1995

Journal of Hematotherapy

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Autologous bone marrow transplantation (ABMT) is widely used to treat hematologic and non-hematologic malignancies. In an attempt to reduce potential neoplastic contamination of the graft, pharmacologic purging with cyclophosphamide derivatives and etoposide (VP16) is often used. Trilineage hemopoietic engraftment is seen following ABMT with VP16-purged bone marrow (BM), but little is known about immune reconstitution in this setting. We studied the in vitro development of natural killer (NK) cells from VP16-purged BM. These cells, defined by phenotypic and functional criteria, undergo rapid regeneration, expansion, and maturation in the presence of interleukin 2 (IL-2). VP16 seems to spare subsets of NK cells, and this cell lineage develops rapidly in VP16-treated BM cultures from patients with acute myelogenous leukemia (AML) and healthy donors. Since relapse rates remain high, immunotherapy following ABMT with purged BM may be useful and should be considered in these patients.

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Section: Resultssupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

In Vitro Effects of Etoposide Purging on Natural Killer Cells

Silva¹,

Ascensāo²

1995

Journal of Hematotherapy

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“…Higher concentrations (1,000 U/ml) or rIL-2 appear to have similar effects [25]. It should also be noted that the short, 1-week treatment of cultures with IL-2 argues against the expansion of a small population of mature CD56+ cells present from the beginning of the culture.…”

Section: Discussionmentioning

confidence: 99%

“…Both after thawing (day 0 of culture) and at weekly intervals, when a sufficient number o f cells accumulated in culture, a standard 5lCr-rcleasc assay [25] was used to evaluate the presence of cytolytic cells derived from CD34+ progenitors. 1 x 10(,t o 2 x 10f' target cells were washed and incubated for 90 min at 37 °C with N a;51CrO; (Du pont, Boston.…”

Section: Cell-mediated Microcytotoxicity Assaymentioning

confidence: 99%

Hematopoietic Origin of Human Natural Killer (NK) Cells: Generation from Immature Progenitors

1993

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Human natural killer (NK) cells originate from bone marrow, but little is known about NK cell progenitors and ontogeny. We studied the phenotype and functional activity of NK cells derived from highly purified human bone marrow CD34+ cells, which exhibited neither lytic activity nor expression of surface antigens characteristic of NK (CD56) or T (CD3) cells. However, when cultured with hematopoietic growth factors or feeder layers for up to 4 weeks, up to 86% functional CD56+ cells were seen in the absence of mature T cell development. CD56+ cells appeared in all cultures at 2 or 3 weeks, with the largest percentage in those exposed to IL·2. These studies demonstrated that NK cells arise ‘in vitro’ from immature bone marrow progenitors and also suggest a separate origin and differentiation pathway for NK and T cells.

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“…We have previously shown that NK cells can be derived from primitive haemopoietic progenitors (Silva and Ascensao, 1995). 4HC purging of BMMNCs allows for maintenance of only the most primitive haemopoietic progenitors destroying populations of committed progenitors and mature cells (Moore, 1991;Rowley et al, 1993), including active NK cells and their late precursors in BM (Cardoso et al, 1992 curve, which is a feature of quite a few immunomodulatory agents. In vitro, Roq exerts its immune cellular effects both on peripheral blood and at the bone marrow progenitor level but with different results on NK cell proliferation and cytolytic activity.…”

Section: Reagentsmentioning

confidence: 99%

Enhanced lymphokine-activated killer cell activity by an immunomodulator, Roquinimex

Vaz

Silva²,

Ascensāo³

1995

Br J Cancer

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Summary Roquinimex (Roq) is an immunomodulator known to stimulate cellular immune responses. It is currently used for immunotherapy after bone marrow transplantation (BMT). One of the major features of this compound is an enhancement of natural killer (NK) cell activity and numbers. We studied the in vitro effect of Roq on human peripheral blood NK and adherent lymphokine-activated killer cell (ALAK) activities. In cultures supplemented with recombinant interleukin 2 (rIL-2) (1000 U ml-') and Roq a significant increase in NK and LAK function was observed without a parallel increase in cell numbers. We also examined the generation of NK cells from human bone marrow (BM) immature progenitors, obtained by purging with 4-hydroperoxycyclophosphamide (4HC). NK cell numbers and activity were both increased when cultures with rIL-2 (10 U ml-') were supplemented with Roq. These results confirm findings obtained in vivo and in vitro in the murine system and suggest that Roq is an active agent on these lymphoid populations. These properties and good tolerability make Roq an attractive tool for immunotherapy.

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Effect of pharmacological purging on natural killer cell number and activity in human bone marrow

Cited by 4 publications

References 41 publications

In Vitro Effects of Etoposide Purging on Natural Killer Cells

In Vitro Effects of Etoposide Purging on Natural Killer Cells

Hematopoietic Origin of Human Natural Killer (NK) Cells: Generation from Immature Progenitors

Enhanced lymphokine-activated killer cell activity by an immunomodulator, Roquinimex

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