Comparative Analysis of CD137 and LPS Effects on Monocyte Activation, Survival, and Proliferation

Langstein, Joachim; Becke, Florian M.; Söllner, Liane; Krause, Gitte; Brockhoff, Gero; Kreutz, Marina; Andreesen, Reinhard; Schwarz, Herbert

doi:10.1006/bbrc.2000.2889

Cited by 52 publications

(31 citation statements)

References 21 publications

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“…Given that similar changes are induced by CD137L signalling in myeloid or monocytic cells during normal myelopoiesis from healthy individuals (Langstein et al, 1998(Langstein et al, , 2000, these observations in AML cells indicate that they can also undergo some degree of differentiation to a more mature phenotype in response to treatment with CD137-Fc protein.…”

Section: Resultsmentioning

confidence: 88%

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CD137 ligand signalling induces differentiation of primary acute myeloid leukaemia cells

et al. 2014

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SummaryCD137 ligand (CD137L), a member of the tumour necrosis factor family, is expressed as a cell surface molecule. Engagement of CD137L on haematopoietic progenitor cells induces monocytic differentiation, and in peripheral monocytes CD137L signalling promotes differentiation to mature dendritic cells. We hypothesized that CD137L signalling would also induce differentiation in transformed myeloid cells. Here we show that recombinant CD137 protein, which crosslinks CD137L and initiates reverse CD137L signalling in myeloid cells, induces morphological changes (adherence, spreading), loss of progenitor markers (CD117), expression of maturation markers (CD11b, CD13) and secretion of cytokines that are indicative of myeloid differentiation. Under the influence of CD137L signalling, acute myeloid leukaemia (AML) cells acquired expression of co-stimulatory molecules (CD80, CD86, CD40), the dendritic cell marker CD83 and dendritic cell activities, enabling them to stimulate T cells. CD137L signalling induced differentiation in 71% (15 of 21) of AML samples, irrespective of French-American-British classification and CD137L expression level. However, the type of response varied with the AML subtype and patient sample. In summary, this study demonstrated that CD137L signalling induced differentiation in malignant cells of AML patients, and suggests that it may be worthwhile to investigate treatment with recombinant CD137 protein as a potential novel therapeutic approach for AML.

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Section: Resultsmentioning

confidence: 88%

“…enhances their survival and proliferation (Langstein et al, 1998(Langstein et al, , 2000. Further, CD137L signalling induces maturation of immature dendritic cells (DC) (Kim et al, 2002;Laderach et al, 2003;Lippert et al, 2008), and even differentiation of peripheral human monocytes to mature DC (Ju et al, 2009;Kwajah & Schwarz, 2010).…”

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confidence: 99%

CD137 ligand signalling induces differentiation of primary acute myeloid leukaemia cells

et al. 2014

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“…In vitro studies, and studies using transgenic mice, have shown that CD137L reverse signals modulate cellular responses in immune cells such as monocytes/macrophages, DC, T cells and B cells, as well as in non-immune cells such as bone marrow cells and carcinoma cells [13]. Ligation of CD137L evokes reverse signals in monocytes and DC, and induces or enhances innate immune responses [14][15][16]. Cross-linking of CD137L with recombinant CD137 protein up-regulates the expression of M-CSF, the primary factor affecting the survival, proliferation, differentiation and function of mononuclear phagocytes [16].…”

Section: Introductionmentioning

confidence: 99%

CD137 ligand‐mediated reverse signals increase cell viability and cytokine expression in murine myeloid cells: Involvement of mTOR/p70S6 kinase and Akt

Kim

Lee

2009

Eur J Immunol

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Cross-linking of CD137 ligand (CD137L), a member of the TNF family, with recombinant CD137-Fc (rCD137-Fc) protein enhanced adherence of bone marrow-derived macrophages, and increased the expression of ICAM-1, IL-1b, IL-6, M-CSF and phosphotyrosine proteins. In RAW264.7 cells, a murine myeloid cell line, rCD137-Fc not only increased adherence but also cell multiplication, in a manner comparable to LPS or M-CSF. In addition, it upregulated expression of IL-1b, IL-1 receptor antagonist, IL-6, COX2, tenascin C, neuropeptide Y and M-CSF mRNA. Neutralization of M-CSF by incubating the RAW264.7 cells with anti-M-CSF mAb did not prevent the CD137L signal-induced viability. Viability was blocked by PP2, an Src tyrosine kinase inhibitor, rapamycin, an mTOR inhibitor and LY294002, a PI3K inhibitor, but not by Wortmannin, another PI3K inhibitor. Cross-linking of CD137L increased phosphorylation of Akt and p70S6 kinase. The latter was blocked by PP2, rapamycin or LY294002, but not by Wortmannin, whereas phosphorylation of Akt was blocked by LY294002 or Wortmannin. These findings demonstrate that reverse signals evoked by CD137L regulate immune functions in macrophages.

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“…Additionally, CD137 is constitutively expressed on primary monocytes and, upon cross-linking with immobilized CD137 ligand, mediates adherence, activation, proliferation, survival, expression of proinflammatory cytokines, and down-regulation of the anti-inflammatory cytokine interleukin-10 (35-37, 40, 53, 56). Furthermore, it has also been demonstrated that CD137 ligand is required for initiation of proliferation of monocytes in response to LPS (34).…”

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GeneChip Analyses of Global Transcriptional Responses of Murine Macrophages to the Lethal Toxin ofBacillus anthracis

Comer¹,

Galindo

Chopra

et al. 2005

Infect Immun

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We performed GeneChip analyses on RNA from Bacillus anthracis lethal toxin (LeTx)-treated RAW 264.7 murine macrophages to investigate global effects of anthrax toxin on host cell gene expression. Stringent analysis of data revealed that the expression of several mitogen-activated protein kinase kinase-regulatory genes was affected within 1.5 h post-exposure to LeTx. By 3.0 h, the expression of 103 genes was altered, including those involved in intracellular signaling, energy production, and protein metabolism

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Comparative Analysis of CD137 and LPS Effects on Monocyte Activation, Survival, and Proliferation

Cited by 52 publications

References 21 publications

CD137 ligand signalling induces differentiation of primary acute myeloid leukaemia cells

CD137 ligand signalling induces differentiation of primary acute myeloid leukaemia cells

CD137 ligand‐mediated reverse signals increase cell viability and cytokine expression in murine myeloid cells: Involvement of mTOR/p70S6 kinase and Akt

GeneChip Analyses of Global Transcriptional Responses of Murine Macrophages to the Lethal Toxin ofBacillus anthracis

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