摘要:

AbstractLymphoid development differs sharply between the primary and secondary lymphoid organs. In the former, lymphocytes arise from precursors by antigen-independent processes under thymic or bone marrow microenvironmental influences and undergo extensive selective processes before being allowed to leave. In the latter, lymphocytes with receptors relevant to particular antigens undergo a second wave of proliferation and differentiation leading to the emergence of immunocytes with effector functions. Each of the two sets of events are profoundly dependent on cellular interactions. In the primary lymphoid organs, the“action”centres on stromal cell-lymphoid precursor interactions, and artificial systems permitting B cell formation are much more advanced than those for T cell development. For B cells, IL-7 andc-kitligand (KL) are clearly important but so are as yet undefined stromal cell-derived activities. For thymic development, only fragments of the complex 3-week process of T cell formation can be mimickedin vitroand no IL has unequivocally been shown to be critical.Within the secondary lymphoid organs, where lymphocytes react to the antigenic universe, the key to regulation lies in interactions between accessory cells (dendritic cells, macrophages and their various relatives) T cells and B cells. Efforts to squeeze the relevant cytokines into sharp compartments such as activation factors, growth factors and differentiation factors have been largely unsuccessful. While we can say a great deal about key players such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IFN-γand TGF-βwhich have many well defined effects, thre is also great excitement about newer bioactivities, some of which require cell membrane preparations and others contact with actual living cells. Despite redundancies in factor action as well as synergistic effects, the prospects for rapid progress in understanding of these post-antigenic factors are bright.

ISSN:0897-7194    

DOI:10.3109/08977199209046407

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractPDGF receptors have recently been found to be expressed in microvascular endotheliumin vivounder circumstances of endothelial cell activation and angiogenesis suggesting that PDGF may have a direct effect on endothelial cells. We have tested the angiogenic activity of PDGF-AA and -BB homodimers in the chick chorioallantoic membranein vivo.PDGF-BB was found to consistently induce an angiogenic response whereas PDGF-AA was less active. Morphological analyses revealed that there was little inflammation associated with this response but an increase in vessel density suggested a direct effect of PDGF on embryonic chorioallantoic endothelial cells.In vitro, PDGF-BB was found to be more potent than PDGF-AA in stimulating the chemotaxis of rat brain capillary endothelial cells. This is consistent with a direct effect of PDGF on endothelial cells. Thus, this novel angiogenic activity of PDGF has implications for several developmental and pathological events in which PDGF, particularly the B-chain, is expressed.

ISSN:0897-7194    

DOI:10.3109/08977199209046408

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractPlatelet-derived growth factor (PDGF) consists of disulfide-linked homo-or heterodimers of A and B chains. mRNA encoding the A chain (PDGF-A) occurs in two versions that differ by the presence or absence of a single short exon. These alternatively-spliced mRNAs encode polypeptides that differ in length by fifteen amino acids. The longer isoform (PDGF-AL) possesses a highly basic carboxy-terminal extension that is responsible for retaining PDGF-ALhomodomers at the cell surface after secretion, while homodimers of the shorter isoform (PDGF-AS) are released into the extracellular medium. We have investigated the mechanism by which PDGF-ALremains in association with the cells that produce it. We expressed epitope-tagged versions of PDGF-ALand PDGF-ASin Cos cells and compared their intra-and extracellular distributions by immunofluorescence microscopy. PDGF-AL, but not PDGF-ASwas detected on and around cells in a diffuse pattern suggesting association with the extracellular matrix (ECM). Metabolically radiolabeled PDGF-AL, but not PDGF-AS, could be eluted from ECM preparations by washing in high salt. Moreover, PDGF-ALbound reversibly to heparin-Sepharosein vitroat physiological salt concentrations, eluting at a salt concentration around 0.5 M. PDGF-ASdid not bind to heparin under the same conditions. Thus, PDGF dimers that contain PDGF-ALmay remain immobilized near the cells that secrete them by virtue of binding to heparin-like constituents of the ECM.

ISSN:0897-7194    

DOI:10.3109/08977199209046409

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractWe used a baculovirus vector/insect host cell system to express cDNA clones of PDGF A genes from mouse and frog (Xenopus laevis). The insect host cells process PDGF A subunits from either frogs or mice into biologically active AA homodimers with yields in the range of 0.5-1.0 mg/liter of culture medium. The recombinant PDGFs can be metabolically labeled with35S-cysteine for use in radioreceptor and radioimmunoassays. Neutralizing polyclonal antisera can be raised against the mouse and frog PDGFs. These antisera are markedly species-specific in action. However, in radioreceptor binding assays and bioassays for mitogenic activity, human, mouse and frog PDGF AA homodimers occupy and activate murine PDGF receptors with equal efficiency.

ISSN:0897-7194    

DOI:10.3109/08977199209046410

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractThe binding of heparin-binding EGF-like growth factor (HB-EGF) to the epidermal growth factor (EGF) receptor of human endometrial carcinoma cells was compared to that of EGF using an125I-EGF radioreceptor assay. The inhibitory effect of HB-EGF on125I-EGF binding was reversed either in the presence of heparin (but not by chondroitin sulfate) or by pre-treating the cells with heparinase. These treatments did not affect the binding of EGF to its receptor. To map potential regions in the HB-EGF molecule that mediate its heparin-dependent interaction with the EGF receptor, HB-EGF peptides were synthesized that were non-homologous to EGF. Accordingly residues 20-25 and 36-41, but not residues 8-19, of HB-EGF were found to be (i) heparin-binding and (ii) modulators of HB-EGF (but not of EGF) binding to the EGF receptor.

ISSN:0897-7194    

DOI:10.3109/08977199209046411

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractWe have shown that tumor necrosis factorα(TNFα) and interleukin 2 (IL-2) are complementary for stimulation of growth of the hematopoietic stem cell line, LyD9. Neither TNFαnor IL-2 alone could stimulate the proliferation of LyD9 cells even after pre-incubation with these growth factors. The number of high-affinity IL-2 receptors on LyD9 cells did not increase after incubation with IL-2 and TNFα. These results suggest that the proliferative response of LyD9 by TNFαand IL-2 is not mediated by receptor inducing activities. We used the induction of the proto-oncogenesc-mycandc-pimto characterize the proliferative stimulation by IL-2 and TNFα. Northern blot analysis revealed that the simultaneous addition of IL-2 and TNFαwas more efficient than IL-2 alone forc-mycmRNA induction. However, the addition of TNFa and IL-2 could not increasec-pimmRNA more than the level induced by IL-2 alone. The results indicate that the two growth factors complement each other by transducing different types of growth signal.

ISSN:0897-7194    

DOI:10.3109/08977199209046412

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractAmphiregulin (AR) is a 23 kDa, bifunctional growth modulating glycoprotein belonging to the epidermal growth factor (EGF) family of polypeptide growth regulators. AR possesses two putative nuclear localization sequences (NLS), binds to DNA sepharose, and localizes to the nucleoli of human ovarian surface epithelial carcinoma cells suggesting that AR has a direct nuclear role. We have found that125I-labeled AR, when exogenously applied to several carcinoma cell lines, associated with nuclei in a time, temperature, and concentration dependent fashion. The control peptide, EGF, also associated with these fractions but at approximately 20% of the effiiciency of AR. Cross-linking experiments with125I-labeled AR and nuclear fractions derived from various carcinoma and normal cell lines demonstrated that AR binds two proteins of molecular mass 205 and 120 kDa. AR binding to these nuclear fraction proteins was specific and saturable as shown by competition experiments utilizing both SV-40 large T antigen NLS and an AR derived peptide encompassing both putative AR NLS. The combined results suggest that nuclear interactions may play a significant role in AR induced growth responses.

ISSN:0897-7194    

DOI:10.3109/08977199209046413

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractRetrovirally expressed human CSF-1 receptor can induce CSF-1-dependent growth of IL-3-dependent hemopoietic cells FDC-P1. Here we show that expression of the human CSF-1 receptor also allowed FDC-P1 cells to grow in response to Insulin-like Growth Factor-1 (IGF-I). The authentic receptor for IGF-I was identified by affinity cross-linking and binding analysis on both control (infected with aneovector) and CSF-1 receptor expressing FDC-P1 cells. DNA and RNA analysis of these cells and of five clones of IGF-I responsive cells demonstrated that the IGF-I receptor gene was not rearranged nor was it abnormally expressed in IGF-I responsive cells. These results suggest that myeloid cells over-expressing CSF-1R (c-fmsprotooncogene product) might have a proliferative advantage over normal myeloid cells in a physiological situation, independently of the presence of CSF-1 or the capacity of the cells to respond to CSF-1. This would indicate a possible role forc-fmsin human neoplasia.

ISSN:0897-7194    

DOI:10.3109/08977199209046414

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

AbstractBasic fibroblast growth factor immunoreactivity (bFGF-IR) was detected in a specific set of nerve cells in the central nervous system of the gull-tapewormDiphyllobothrium dendriticum(Cestoda)—an obligatory endoparasite. The long varicose processes of the bFGF-IR neurons extend along the two main nerve cords, which contain an actively growing population of nerve cells. A neurotrophic function for the bFGF-like material is proposed. The adult tapeworm lives in the intestine of a homeothermic host and has a pattern of very active and never ending growth. The larval stages live in poikilothermic hosts and grow very slowly. The bFGF-IR nerve cells occur both in II stage larvae and in adult worms. Thus, no correlation between the presence of bFGF-IR and the general growth rate of the worm was found. Western blot analysis revealed the presence of an anti-bFGF immunoreactive peptide with a molecular mass of 47 kDa in both larval and adult worms.

ISSN:0897-7194    

DOI:10.3109/08977199209046415

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor