摘要:

AbstractNew projects are always exciting, but often their worth can only be judged over many years.Growth Factorsis a new project and it has been exciting to participate in these initial phases. The response from my fellow editors and the members of the Editorial Board has been unreservedly enthusiastic. Of course, we all hesitated long enough to ask the question why another journal? The simple answer is that we are all committed to research into growth factors and we perceived that interest in this field of research is growing at a rapid rate. Without compromising quality, we wanted a forum for research on growth factors to be communicated as quickly as possible. Harwood Academic Press offered us this opportunity.

ISSN:0897-7194    

DOI:10.3109/08977198809000241

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractEndothelial cells, including human umbilical vein endothelial cells (HUVEC), bovine aortic endothelial cells (BAEC), and bovine capillary endothelial cells (BCEC) in culture synthesize basic fibroblast growth factor (bFGF) and transforming growth factor type beta (TGF-beta). Basic FGF was cell-associated and synthesis was demonstrated by (i) the presence of bFGF mRNA species, (ii) binding to heparin-Sepharose and elution at 1.5 M NaCI, (iii) cross-reactivity with anti-bFGF antibodies when analyzed by electrophoretic blotting, and (iv) biological activity. Basic FGF was found in cell lysates at 2.3 ng/306cells in HUVEC, 2.0 ng/106cells in BCEC, and 13 ng/106cells in BAEC. TGF-beta was secreted into media, and synthesis was demonstrated by (i) presence of TGF-beta mRNA species, (ii) cross-reactivity with anti-TGF-beta antibodies when analyzed by immunoprecipitation, (iii) competitive binding with authentic human platelet-derived TGF-beta that was blocked by TGF-beta specific blocking antibodies, and (iv) inhibition of [3H]TdR incorporation in CCI-64 cells. TGF-beta was secreted in an inactive form and required acid activation for detection. HUVEC synthesized 2.0 ng TGF-beta/106cells per 12 hr; BCEC, 3.5 ng; and BAEC, 3.5 ng. HUVEC proliferation was not affected by treatment with exogenous TGF-beta, while BCEC proliferation was decreased by treatment with TGF-beta. Vascular endothelium is thus a source for these two potent multifunctional regulatory molecules, both of which may affect the growth of endothelium and neighboring fibroblasts, smooth muscle cells and white blood cells. The activation or release of these factors by endothelium may be a precipitating event in important cellular processes such as wound healing, organogenesis, and angiogenesis.

ISSN:0897-7194    

DOI:10.3109/08977198809000242

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractWe report here that transforming growth factor-β1 (TGF-β1) inhibits platelet-derived growth factor (PDGF)-induced DNA synthesis in normal human fibroblasts in a cell density-dependent manner; no inhibition was seen in sparse cultures, approximately 50% inhibition in confluent cell cultures, and an almost total inhibition in dense cultures. The PDGF-inducible genesc-mycandc-foswere induced also by TGF-β1. Simultaneous addition of TGF-PI and PDGF resulted in sustained, rather than transient, expression ofc-fosmRNA; c-fosmRNA was detected as long as 24 hr after addition of PDGF and TFG-β1. TGF-β1 also induced mRNA for the A chain, but not the B chain, of PDGF. Conversely, PDGF induced TGF-β1 mRNA in sparse but not in dense cultures. These data indicate the existence of a complex interdependent regulation of PDGF and TGF-βmRNA expression which is influenced by the cell density.

ISSN:0897-7194    

DOI:10.3109/08977198809000243

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractThe kinetic parameters involved in determining the steady-state interaction of Multi-CSF with FDCP-1 cells at 37°C have been determined by kinetic analysis under steady-state conditions and by curve-fitting the rate of approach to steady-state conditions. The two methods are in substantial agreement and yield values of Vr=28 receptors/cell/min for the rate of appearance of receptors at the cell surface,keandki=0.061 min−1and 0.0044 min−1for the rate constants of internalization of occupied and unoccupied receptors, respectively,kh=0.008 min−1for the rate constant of degradation of internalized ligand, ka=2.9×108M−1min−1for the rate constant of association andkd=0.11 min−1for the rate constant of dissociation of ligand with receptor. Analysis of steady-state conditions indicated that Multi-CSF caused substantial down-regulation of surface receptors and that considerably more Multi-CSF was inside the cell than at the cell surface. The implications of these results for utilization rates of Multi-CSF by FDCP-1 cells and the relationship of receptor occupancy to biological activity are discussed.

ISSN:0897-7194    

DOI:10.3109/08977198809000244

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractThe binding, internalization and degradation rates of three different murine colony-stimulating factors (Multi-CSF or interleukin-3, GM-CSF and G-CSF) and their receptor turnover rates were determined for normal bone marrow cells and a number of different cell lines at 37°C. The kinetic parameters were extracted from a curve-fitting analysis of the approach to steady-state of surface-bound and internalized CSFs by methods described by Myers et al. (1987). The primary binding kinetic constants (association and dissociation) for each CSF on different cell types were similar, suggesting a single type of receptor for each CSF. In all cases, CSF binding induced a faster rate of internalization of occupied receptors than unoccupied receptors and resulted in significant accumulation of CSF inside the cell under steady-state conditions. The steady-state constant, determining the relationship between CSF concentration and receptor occupancy, indicated that, in all cases, more receptors were occupied at a given CSF concentration under steady-state conditions than would be under equilibrium conditions. Nevertheless, the data predicted that maximal biological effects of the CSFs were exerted at concentrations that did not result in full receptor occupancy. Comparison of the kinetic constants derived for the same CSF interacting with different types of cells or different CSFs interacting with the same cell type indicated that CSF and receptor processing resulted from a dynamic interplay of receptor-determined and cell-determined events. This resulted in a flexibility of the kinetic parameters that matched the variety of biological responses elicited by CSFs in different cell types.

ISSN:0897-7194    

DOI:10.3109/08977198809000245

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractWe isolated the chromosomal gene for mouse interleukin-5 (IL-5) from genomic libraries using a cloned mouse IL-5 cDNA as probe. Nucleotide sequence determination of the IL-5 gene and its flanking regions showed that the gene was composed of four exons. The sequence homologies of the exons 1, 2, 3, and 4 of the human and murine IL-5 genes are 70, 79, 85, and 77%, respectively. TATA-like and CAAT-like sequences were found 25 and 52 base-pairs, respectively, upstream of the transcription initiation site which was identified by S1 mapping analysis. The nucleotide sequences of the mouse and human IL-5 genes were about 70% homologous in the 5′-flanking region extending to 200 base-pairs upstream of the transcription initiation site, beyond which the homology declined rapidly. The sequence surrounding 50 base-pairs upstream of the initiation site was conserved among genes for other lymphokines: such as mouse granulocyte/macrophage colony stimulating factor, mouse IL-2. and mouse IL-4.

ISSN:0897-7194    

DOI:10.3109/08977198809000246

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractRetrovirus vectors provide an efficient carrier for introducing a gene into hematopoietic stem cells although expression of the inserted gene is not always successful. We constructed and compared three retrovirus vectors which carried cDNA encoding the light chain (Tac) of the interleukin 2 receptor under the control of different promoters; long terminal repeat (LTR) of murine retroviruses, the early promoter of simian virus 40 (SV40) and the promoter of the class I antigen gene of the major histocompatibility complex. We made three constructs containing these promoters. A first construct did not contain any additional promoter but LTR. A second and a third constructs contained the SV40 and the class I antigen gene promoters, respectively, in addition to LTR. The LTR of retrovirus vectors is derived from MoMuLV except that the U3region of the 3′LTR of the third construct is derived from myeloproliferative sarcoma virus (MPSV). The second and third constructs were used for infection of bone marrow stem cells as the first construct was less efficient in expression of the interleukin 2 receptor in fibroblasts. Hematopoietic stem cells infected with the recombinant viruses were transplanted into lethally irradiated mice, and the expression of the transduced gene in hematopoietic progenitor cells was analyzed. Analysis of RNA isolated from spleen colonies showed that substantial amounts of interleukin 2 receptor mRNA were made by the construct containing the class I gene promoter and MPSV LTR. However, we could not detect any transcripts from the constructs containing MoMuLV LTR and SV40 early region promoter.

ISSN:0897-7194    

DOI:10.3109/08977198809000247

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractThe work reported here clearly demonstrates that a specific growth factor, interleukin-3 (IL-3), which acts on multipotent haemopoietic stem cells as well as on committed myeloid progenitor cells of different lineages (Schrader, 1988; Whetton and Dexter, 1986), specifically induces a modification of the physical state (“fluidity”) of the cell membranes of two IL-3–responsive and apparently normal haemopoietic cell lines. Furthermore, in a derived IL-3 independent myeloid leukaemic cell line, no such physical response to IL-3 binding was observed. The rapidity of the“normal”response suggests further that it may be associated with, or even constitute per se a critical early effect elicited by IL-3 in sensitive cells, the necessity for which is abrogated in the malignant derivative.

ISSN:0897-7194    

DOI:10.3109/08977198809000248

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractWhile screening neuropeptides for activity as growth factors we have found that bradykinin is a mitogen for Swiss 3T3 cells. It acts synergistically with insulin, and maximal effect is obtained at 10 nM. It acts through a distinct receptor, characterized as a B, subtype using bradykinin analogues. The neuropeptides bombesin and vasopressin are also potent mitogens for Swiss 3T3 cells. The substance P antagonists [DArg1, DPro2, DTrp7,9, Leu11] substance P and (DArg1, DPhe5, DTrp7,9, Leu11] substance P are inhibitors of DNA synthesis stimulated by both bombesin and vasopressin. In the present study they were found also to inhibit bradykinin-induced mitogenesis. In contrast, the ligand-specific antagonists [Leu13-Ψ(CH2NH)Leu14]bombesin, [Pmp1, OMeTyr2, Arg8]vasopressin and [DArg11, Hyp3, Thi3,8, DPhe7]bradykinin showed no cross-inhibition with each others receptors. We propose therefore that the receptors for the mitogenic neuropeptides bombesin, vasopressin, and bradykinin can interact with two classes of antagonist, one recognizing the ligand binding site (e.g., [Leu13-Ψ(CH2NH)Leu14]bombesin) and the other recognizing a common domain shared by the three receptors (e.g., [DArg1, DPhe5, DTrP7,9, Leu11] substance P).

ISSN:0897-7194    

DOI:10.3109/08977198809000249

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractTumor-promoting phorbol ester derivatives are known to stimulate as well as inhibit the cell cycle traverse of many kinds of cells, but it is not known whether or how these effects are related to tumor promotion. It is shown here that the potency of the phorbol diester PMA (phorbol myristate acetate) to cause a delay of cell division depends on the cell cycle position at the beginning of exposure to the PMA. Quiescent human fibroblasts were stimulated with epidermal growth factor, and PMA was added to the cultures at different times after stimulation. The later PMA was added, the stronger was the mitotic delay it caused. This means that cells which become exposed while they are in an early stage of the cycle are less effectively delayed and reach mitosis earlier than those for which exposure begins at a later stage of the cycle. The data indicate that PMA is actually able to reverse the order in which the cells of a normally growing population divide. In organized tissues this could disturb the intercellular communication which may be linked to the relative cell cycle positions of neighboring cells.

ISSN:0897-7194    

DOI:10.3109/08977198809000250

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor