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  • 1
    Electronic Resource
    Electronic Resource
    Innervation and neurokinin receptors during angiogenesis in the rat sponge granuloma (1996)
    Springer
    Journal of molecular histology 28 (1996), S. 759-769 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Angiogenesis is an essential component of wound healing and inflammation. In the rat subcutaneous sponge implantation model, angiogenesis can be enhanced by administration of the sensory neuropeptide, substance P. We have used quantitativein vitro receptor autoradiography and immunohistochemistry to investigate the development of endogenous neurovascular regulatory systems in the newly-formed granulation tissue of this model. The fraction of endothelial cells immunoreactive for proliferating cell nuclear antigen, endothelial fractional area, and133Xe clearance were used as measures of endothelial proliferation, neovascularization, and blood flow, respectively. Endothelial proliferation occurred predominantly in tissues surrounding the sponge, and peaked before neovascularization of sponge stroma and the establishment of sponge blood flow. Substance P-containing sensory nerves and specific, high affinity substance P binding sites with characteristics of neurokinin receptors of the NK1 subclass, were localized to microvessels surrounding the sponge at all time points. Lower density substance P binding sites were localized to newly formed microvessels within the sponge stroma, progressively increasing in density from day 4 to day 14. Nerve fibres were observed in the stroma of only 2 of 6 sponges at day 14, and none at earlier time points. These data support the hypothesis that substance P-enhanced angiogenesis in this model results from a direct action on microvascular NK1 receptors. Neovascularization is a sequential process, with early endothelial proliferation followed by new vessel formation and increased blood flow, with maturation of endogenous neurovascular regulatory systems occurring late in this process in inflamed tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02272149
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Inhibition of angiogenesis in rats by IL-1 receptor antagonist and selected cytokine antibodies (1994)
    Springer
    Inflammation 18 (1994), S. 45-58 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Daily administration of 50 ng recombinant human interleukin 1-alpha (IL-1α), 25 ng IL-8, 50 ng tumor necrosis factor-alpha (TNF-α), or 100 ng basic fibroblast growth factor (bFGF) caused intense neovascularization in a rat sponge model. These cytokine-induced neovascular responses were inhibited by coadministration of IL-1 receptor antagonist (IL-1ra; 50 μg), IL-8 antiserum (IL-8-AS; 1∶1000), TNF-α antibody (TNF-AB; 500 ng), or a monoclonal antibody to bFGF (DG2; 1000 ng), respectively. These data suggest that it is possible to manipulate the angiogenic response elicited by a defined cytokine by its receptor antagonist or neutralizing antibody. In the absence of exogenous cytokines, the sponge-induced angiogenesis was profoundly suppressed by dexamethasone (5μg/day), but not modified by IL-1ra, IL-8-AS, TNF-AB, and DG2 alone. However, the combination of these four reagents was able to inhibit the sponge-induced neovascular response almost completely. These findings provide direct evidence that IL-1α, IL-8, TNF-α and/or bFGF have an intrinsic role in angiogenesis. Further work is necessary to characterize the profile of these cytokines during angiogenesis and to elucidate the nature of their interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01534597
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Protein kinase C inhibitor calphostin C prevents cytokine-induced angiogenesis in the rat (1995)
    Springer
    Inflammation 19 (1995), S. 39-54 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A rat sponge implant model was used to examine the role of protein kinase C (PKC) in angiogenesis, Neovascular response was determined by measurements of relative sponge blood flow by a133Xe clearance technique and confirmed histologically. Morphometric analysis was used to quantitate the amount of fibrovascular growth in the sponges. Daily doses of recombinant human basic fibroblast growth factor (bFGF, 100 ng), tumor necrosis factor-alpha (TNF-α, 50 ng), or interleukin1-alpha (IL-1α, 50 ng) caused neovascular responses that were blocked by daily coadministration of the selective PKC inhibitor, calphostin C (4μg). To confirm that calphostin C was able to inhibit PKC in vivo, its effect on the angiogenic response elicited by the PKC activator, phorbol 12-myristate 13-acetate (PMA, 30μg) was examined. The blood flow and morphometric data clearly showed that the intense neovascularization induced by PMA was totally suppressed by coadministration of calphostin C (4μg). Thus, these results suggest that cytokine-induced angiogenesis may be mediated in part through the activation of PKC and that selective inhibition of this enzyme could have therapeutic benefit in angiogenic diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01534379
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Interleukln-8 stimulates angiogenesis in rats (1993)
    Springer
    Inflammation 17 (1993), S. 135-143 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To test the hypothesis that the cytokines interleukin-6 (IL-6) and IL-8 may play regulatory roles in the aberrant neovascularization in chronic inflammatory diseases, we examined their effects in a rat sponge model and compared their actions with those of IL-1 and lumor necrosis factor-α (TNF-α). Daily doses of 3 pmol IL-8, IL-1, TNF-α, but nol IL-6, significantly accelerated the sponge-induced angio-genesis. Although lower doses (0.3 pmol) of these cytokines were inactive, IL-1 acted synergistically with subthreshold daily doses (10 pmol) of substance P (SP) and bradykinin (BK) to produce an intense angiogenic response. In contrast, IL-8 only interacted positively with IL-1, but not TNF-α, SP, or BK. There was no synergism or antagonism between IL-6 and SP. These results demonstrate the discrete interactions between angiogenic factors and cytokines in chronic inflammation and suggest that the sponge model is a good means for the study of such interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00916100
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    Paper (German National Licenses)
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