New phenotypic, functional and electrophysiological characteristics of KG-1 cells

Hajas, György; Zsiros, Emese; László, Tünde; Hajdú, Péter; Somodi, Sándor; Réthi, Bence; Gogolák, Péter; Ludányi, Katalin; Panyi, György; Rajnavölgyi, Éva

doi:10.1016/j.imlet.2003.11.021

Cited by 12 publications

(15 citation statements)

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“…The presence of an outward rectifying K ϩ conductance was described in DCs isolated from murine spleen (2), but the ion channel responsible for that current was not identified. The expression Ca 2ϩ -activated K ϩ channels of IKCa1 type were described in the KG-1 erythroleukemia cell line that possesses numerous characteristics of human DCs (44). A recent study showed the existence of Kv1.3-like and Kv1.5 currents in MDCs of the CNS (36).…”

Section: Discussionmentioning

confidence: 99%

Developmental Switch of the Expression of Ion Channels in Human Dendritic Cells

Zsiros

Kis-Tóth

Hajdú

et al. 2009

The Journal of Immunology

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Modulation of the expression and activity of plasma membrane ion channels is one of the mechanisms by which immune cells can regulate their intracellular Ca2+ signaling pathways required for proliferation and/or differentiation. Voltage-gated K+ channels, inwardly rectifying K+ channels, and Ca2+-activated K+ channels have been described to play a major role in controlling the membrane potential in lymphocytes and professional APCs, such as monocytes, macrophages, and dendritic cells (DCs). Our study aimed at the characterization and identification of ion channels expressed in the course of human DC differentiation from monocytes. We report in this study for the first time that immature monocyte-derived DCs express voltage-gated Na+ channels in their plasma membrane. The analysis of the biophysical and pharmacological properties of the current and PCR-based cloning revealed the presence of Nav1.7 channels in immature DCs. Transition from the immature to a mature differentiation state, however, was accompanied by the down-regulation of Nav1.7 expression concomitant with the up-regulation of voltage-gated Kv1.3 K+ channel expression. The presence of Kv1.3 channels seems to be common for immune cells; hence, selective Kv1.3 blockers may emerge as candidates for inhibiting various functions of mature DCs that involve their migratory, cytokine-secreting, and T cell-activating potential.

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Section: Discussionmentioning

confidence: 99%

Developmental Switch of the Expression of Ion Channels in Human Dendritic Cells

Zsiros

Kis-Tóth

Hajdú

et al. 2009

The Journal of Immunology

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“…We and others have also shown that these myeloid blasts are not immunostimulatory when undifferentiated, but when differentiated with cytokines or phorbol esters (PMA), result in APCs that have characteristic DC markers (MHC I and II, CD40, CD80, CD86, and CD83), expression of DC-specific molecular markers (eg, DC-CK1, DC-STAMP), and unique DC function (eg, the ability to cross-present antigen, potently activate T cells to a significantly greater degree compared with normal monocytes, etc). 35,36,36,[49][50][51][52][53][54][55] We first characterized the effect of DCs on myeloma cell proliferation. Proliferation of 8226 ( Figure 7A; left panel) and U266 ( Figure 7A; right panel) was not affected when cocultured with irradiated, undifferentiated K562.…”

Section: Coculture With Dcs Modulates Myeloma Cell Proliferation and mentioning

confidence: 99%

CD28-mediated regulation of multiple myeloma cell proliferation and survival

Bahlis

King

Kolonias

et al. 2007

Blood

119

115

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Although interactions with bone marrow stromal cells are essential for multiple myeloma (MM) cell survival, the specific molecular and cellular elements involved are largely unknown, due in large part to the complexity of the bone marrow microenvironment itself. The T-cell costimulatory receptor CD28 is also expressed on normal and malignant plasma cells, and CD28 expression in MM correlates significantly with poor prognosis and disease progression. In contrast to T cells, activation and function of CD28 in myeloma cells is largely undefined. We have found that direct activation of myeloma cell CD28 by anti-CD28 mAb alone induces activation of PI3K and NFB, suppresses MM cell proliferation, and protects against serum starvation and dexamethasone (dex)-induced cell death. Coculture with dendritic cells (DCs) expressing the CD28 ligands CD80 and CD86 also elicits CD28-mediated effects on MM survival and proliferation, and DCs appear to preferentially localize within myeloma infiltrates in primary patient samples. Our findings suggest a previously undescribed myeloma/DC cell-cell interaction involving CD28 that may play an important role in myeloma cell survival within the bone marrow stroma. These data also point to CD28 as a potential therapeutic target in the treatment of MM. IntroductionMultiple myeloma (MM) remains an incurable clonal B lymphoid neoplasm of plasma cells, second only to non-Hodgkin lymphoma in incidence. 1 Despite significant initial responses to chemotherapy, more than 90% of patients with MM relapse with resistant disease, 2 underscoring the need to identify novel therapeutic targets that affect myeloma survival and resistance pathways. Given that MM cells are critically dependent on normal elements of the bone marrow stroma for cell growth and survival, these interactions are attractive targets. One such interaction is stromal production of soluble growth factors, such as IL-6 and TRANCE. 1,3 Another important set of interactions involves direct myeloma cell contact with extracellular matrix (ECM) and/or stromal cells. Such direct contact up-regulates stromal cell IL-6 and VEGF production, induces NFB signaling, drops myeloma cells out of cell cycle, and enhances resistance to chemotherapy. [4][5][6] However, the specific molecular (eg, integrins 4,7 ) and cellular components (eg, osteoclasts 8 ) of these direct interactions within the complex bone marrow microenvironment are only beginning to be described. As important, the characteristic progression of myeloma to stromal independence marks a clinically worse disease, 9 yet the mechanisms that underlie this transition are also poorly understood.Identification of prosurvival receptors typically expressed on myeloma cells may point to the stromal cells expressing the receptor ligands. One potential receptor is CD28. CD28 has a restricted lineage expression, found predominantly on T cells but also on normal plasma cells, primary myeloma isolates, and myeloma cell lines at levels comparable with T cells. [10][11][12][13] In T cells, CD28 recep...

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“…DC-CK1 and DC-STAMP) and function (e.g. cross-presentation of antigen) (27,35,36,(51)(52)(53)(54)(55). KG1a is a less differentiated cell line spontaneously derived from KG1 and does not differentiate in response to phorbol esters (27,56,57).…”

Section: Pkc-␤ii Is Specifically Activated By DC Differentiation Signmentioning

confidence: 99%

Protein Kinase C βII Plays an Essential Role in Dendritic Cell Differentiation and Autoregulates Its Own Expression

Cejas

Carlson²,

Zhang

et al. 2005

Journal of Biological Chemistry

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Dendritic cells (DC) arise from a diverse group of hematopoietic progenitors and have marked phenotypic and functional heterogeneity. The signal transduction pathways that regulate the ability of progenitors to undergo DC differentiation, as well as the specific characteristics of the resulting DC, are only beginning to be characterized. We have found previously that activation of protein kinase C (PKC) by cytokines or phorbol esters drives normal human CD34؉ hematopoietic progenitors and myeloid leukemic blasts (KG1, K562 cell lines, and primary patient blasts) to differentiate into DC. We now report that PKC activation is also required for cytokinedriven DC differentiation from monocytes. Of the cPKC isoforms, only PKC-␤II was consistently activated by DC differentiation-inducing stimuli in normal and leukemic progenitors. Transfection of PKC-␤II into the differentiation-resistant KG1a subline restored the ability to undergo DC differentiation in a signal strength-dependent fashion as follows: 1) by development of characteristic morphology; 2) the up-regulation of DC surface markers; 3) the induction of expression of the NFB family member Rel B; and 4) the potent ability to stimulate allo-T cells. Most unexpectedly, the restoration of PKC-␤II signaling in KG1a was not directly due to overexpression of the transfected classical PKC (␣, ␤II, or ␥) but rather through induction of endogenous PKC-␤ gene expression by the transfected classical PKC. The mechanism of this positive autoregulation involves up-regulation of PKC-␤ promoter activity by constitutive PKC signaling. These findings indicate that the regulation of PKC-␤II expression and signaling play critical roles in mediating progenitor to DC differentiation.

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New phenotypic, functional and electrophysiological characteristics of KG-1 cells

Cited by 12 publications

References 50 publications

Developmental Switch of the Expression of Ion Channels in Human Dendritic Cells

Developmental Switch of the Expression of Ion Channels in Human Dendritic Cells

CD28-mediated regulation of multiple myeloma cell proliferation and survival

Protein Kinase C βII Plays an Essential Role in Dendritic Cell Differentiation and Autoregulates Its Own Expression

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