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J L Cleveland

Publications and source records attributed to J L Cleveland.

116 records · Page 7Linked to original sources
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Serum suppresses myeloid progenitor apoptosis by regulating iron homeostasis.

The growth and survival of committed hematopoietic progenitors is dependent upon cytokine signaling. However, serum is also required for optimal growth of these progenitors in culture ex vivo. Here we report that serum withdrawal leads to myeloid progenitor cell apoptosis. Although serum deprivation-induced cell death has many hallmarks typical of apoptosis, these cell deaths were not inhibited by hemopoietins, survival factors such as IGF-I, or treatment with a broad-spectrum caspase inhibitor. Rather, apoptosis due to serum withdrawal was associated with damage to mitochondria. Surprisingly the serum factor required for myeloid cell survival was identified as iron, and loss of iron led to marked reductions in ATP production. Furthermore, supplementing serum-deprived myeloid cells with bound or free iron promoted cell survival and prevented mitochondrial damage. Therefore, serum suppresses hematopoietic cell apoptosis by providing an obligate source of iron and iron homeostasis is critical for proper myeloid cell metabolism and survival.

Adenosine Triphosphate↗
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Abrogation of IL-3 and IL-2 dependence by recombinant murine retroviruses expressing v-myc oncogenes.

Several oncogenes are thought to cause transformation by affecting the signal transmission pathway of growth factors. One example is the induction of c-myc, the cellular homologue of the avian transforming oncogene v-myc, by platelet-derived growth factor (PDGF) among a set of genes associated with competence induction in fibroblasts. Another of the competence genes, r-fos, has been shown to be related to v-fos, the transforming gene of the FBJ sarcoma virus. In addition, PDGF induces c-fos, the cellular homologue of v-fos. The importance of c-myc induction is suggested by the observation that c-myc, under the control of a glucocorticoid regulator, can partially relieve the requirement of fibroblasts for PDGF. We have examined the effects of oncogenes on haematopoietic/lymphoid cell differentiation, immortalization and factor dependence for growth. Here we report the effects of recombinant murine retroviruses capable of expressing the avian v-myc. With interleukin-3 (IL-3)- or interleukin-2 (IL-2)-dependent cells, the viruses abrogated the requirement for growth factors and suppressed c-myc expression.

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Selective immortalization of murine macrophages from fresh bone marrow by a raf/myc recombinant murine retrovirus.

Myeloid precursors can be grown in vitro in the presence of specific growth factors; however, their expansion is limited by a competing process of terminal differentiation. Proto-oncogenes seem to be involved in cellular proliferation and/or differentiation and may also play a role in the myelopoietic process. Murine myeloid precursors which are grown in vitro with growth factors respond with augmented self-renewal upon infection with recombinant retroviruses carrying the v-myc or v-src oncogenes, suggesting a synergism or complementation between some viral oncogenes (v-onc) and certain growth factors. We now show that the combination of two v-onc genes (raf and myc) induces the selective proliferation of monocytic cells from fresh murine bone marrow (BM) in the absence of a specific growth factor supplement. Depending on the culture conditions these cells can either differentiate and cease to proliferate or grow continuously, thus mimicking the alternative pathways that can be followed by committed BM stem cells in vivo.

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PubMedDate not supplied

Regulation of T cell receptor gamma gene expression by cytokines in murine hematopoietic cells.

Murine IL-3-dependent myeloid cell lines express transcripts from non-rearranged TCR gamma genes and this expression is dependent upon IL-3. To investigate this observation in general terms we examined various IL-3 dependent cell lines for TCR gamma gene expression. We also examined various cytokines to test their potential to induce TCR gamma gene expression. All IL-3 dependent cell lines expressed TCR gamma transcripts. The IL-3 induced expression was sensitive to protein synthesis inhibitors. This demonstrated that the TCR gamma genes belong to the early growth factor response class. IL-3, IL-4, GM-CSF and Erytropoietin (EPO), but not G-CSF, induced TCR gene expression. 32D cells transfected with the IL-2 beta chain receptor became responsive to IL-2 as a growth factor and induced TCR gamma gene expression. The induction of TCR gamma gene expression by the cytokines was not correlated to their growth promoting activity. This indicated different signaling pathways.

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