Development of Inflammatory Angiogenesis by Local Stimulation of Fas In Vivo

Biancone, Luigi; Martino, Antonella De; Orlandi, Viviana Teresa; Conaldi, Pier Giulio; Toniolo, Antonio; Camussi, Giovanni

doi:10.1084/jem.186.1.147

Cited by 118 publications

(71 citation statements)

References 21 publications

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“…Interestingly, agonistic CD95-specific antibodies have been reported to induce local inflammation and neoangiogenesis when implanted subcutaneously in matrigel, in the presence of heparin. 38 Whether local expression of CD95L in similar conditions may also exert such proangiogenic effects is an important question that remains to be investigated. Indeed, because several tumors express CD95L, 13 and because tumor neovascularization is essential for cancer growth and spread, 39 the local response of endothelial cells to CD95L-proliferation or death-may be of major importance in determining cancer progression.…”

Section: Discussionmentioning

confidence: 99%

CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications

Janin

Deschaumes

Daneshpouy

et al. 2002

Blood

107

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Fas (CD95) is a death receptor involved in apoptosis induction on engagement by Fas ligand (CD95L). Although CD95L-mediated apoptosis has been proposed as a pathogenic mechanism in a wide range of diseases, including graft-versushost disease, systemic CD95 engagement in mice by agonistic CD95-specific antibodies or by soluble multimeric CD95L (smCD95L), though lethal, has been reported to cause apoptosis only in a limited range of cell types, that is, hepatocytes, hepatic sinusoidal endothelial cells, and lymphocytes. Another member of the tumor necrosis factor (TNF)/CD95L family, TNF-␣, induces disseminated vascular endothelial cell apoptosis, which precedes apoptosis of other cell types and lethal multiorgan failure. Here we show that systemic CD95 engagement in vivo by agonistic CD95-specific antibody or smCD95L causes rapid, extensive, and disseminated endothelial cell apoptosis throughout the body, by a mechanism that does not depend on TNF-␣. Disseminated endothelial cell apoptosis was also the first detectable lesion in a murine model of acute tissue damage induced by systemic transfer of allogeneic lymphocytes and did not occur when allogeneic lymphocytes were from CD95L-defective mice. IntroductionThe Fas (CD95) protein is a cell surface receptor belonging to the tumor necrosis factor (TNF) receptor family that transduces death signaling on engagement by multimeric Fas ligand (CD95L), either in its membrane-bound form or in its soluble form resulting from cleavage by a putative metalloproteinase. 1,2 Apoptosis induced by inappropriate or excessive expression of CD95L has been proposed as an important pathogenic mechanism in several diseases, involving various organs, tissues, and cell types, and including acute hepatitis, 1,3,4 acute graft-versus-host disease (aGVHD), 5-7 organspecific autoimmune diseases, 8,9 allergic 10 and toxic 11 cutaneous diseases, systemic tissue damage caused by lymphomas and leukemias, 12 and tumor progression. 13 On the other hand, systemic CD95 engagement induced in the mouse by agonistic CD95-specific antibodies or by soluble multimeric CD95L (smCD95L), though lethal, has been reported to cause tissue damage in a limited range of organs, that is, the liver and the lymphoid organs, through apoptosis induction in only 3 cell types, specifically, hepatocytes, 3,14-16 hepatic sinusoidal endothelial cells, 14,17 and lymphocytes. 16,18 A possible explanation for this discrepancy may be that several diseases in which a role for CD95L-induced apoptosis has been proposed in fact require additional facilitating or effector mechanisms that are not induced in these murine models of systemic CD95 engagement. Alternately, these murine models may involve apoptosis induction in additional cell types and tissues that have not yet been identified. The latter possibility could be consistent with 2 previous reports of sinusoidal endothelial cell death in the hemorrhagic liver of mice injected with agonistic CD95-specific antibodies. 14,17 Although this may be an indirect consequence of the com...

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Section: Discussionmentioning

confidence: 99%

CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications

Janin

Deschaumes

Daneshpouy

et al. 2002

Blood

107

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“…The data are less clear on the role of death receptors and their ligands. While it appears that Fas and FasL regulate angiogenesis in the retina of adult animals (Kaplan et al, 1999), it is clear that soluble FasL can also induce an inflammatory angiogenesis in Matrigel plugs in vivo (Biancone et al, 1997). Similarly, TNFa induces angiogenesis in vivo (Friedlander et al, 1995), and may contribute to inflammatory angiogenesis, such as that seen in rheumatoid arthritis (Walsh and Pearson, 2001).…”

Section: Ecm Influences Cell Responses To Other Apoptotic Triggersmentioning

confidence: 99%

Apoptotic cues from the extracellular matrix: regulators of angiogenesis

2003

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A variety of factors cooperate to regulate neovessel formation and persistence. Proangiogenic growth factors have remained an area of intense interest due to their capacity to promote endothelial cell (EC) proliferation and to initiate the angiogenic program. These growth factors are associated with increased cell survival, yet paradoxically, angiogenic ECs are more susceptible to apoptosis than quiescent ECs. Survival is regulated by cooperation between growth factor receptors and integrins, which are in turn governed by the composition of the local extracellular matrix (ECM). Integrin-mediated signaling is altered or disrupted by the presence of soluble, rather than matrix-bound ligands, thus providing a means by which ECM remodeling can influence both integrinand growth factor-mediated events. Ultimately, the collaboration of these factors determines whether ECs survive or die, thereby regulating neovascularization.

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“…This protein family includes other death receptors such as the TNF receptor-1, as well as the nerve growth factor receptor and the costimulatory molecule CD40 (3). CD95 itself has been reported to express diverse functions apart from apoptosis, including a costimulatory effect that potentiates the response to weak TCR signals (4), the induction of angiogenesis (5), and the activation of various tyrosine kinases (6 -9).…”

Section: Cd95/fas Signaling In T Lymphocytesmentioning

confidence: 99%

CD95/Fas Signaling in T Lymphocytes Induces the Cell Cycle Control Protein p21cip-1/WAF-1, Which Promotes Apoptosis

Hingorani¹,

Dao

et al. 2000

The Journal of Immunology

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Ligation of CD95 on T lymphocytes resulted in the up-regulation of a cell cycle control protein, p21cip-1/WAF-1, an inhibitor of cyclin-dependent kinases. This up-regulation was completely blocked by the cysteine protease inhibitor Z-VAD-fmk (benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone), whereas DEVD-CHO (succinyl-Asp-Glu-Val-Asp-aldehyde), a caspase 3 inhibitor, had no effect. In Faslpr-cg mice, a point mutation in the death domain of CD95 results in failure to recruit FADD (Fas-associated death domain), and in the present study this mutation prevented both CD95-mediated apoptosis and p21cip-1/WAF-1 induction. During apoptotic cell death due to irradiation, p21cip-1/WAF-1 is up-regulated by a p53-dependent pathway that responds to DNA damage. However, CD95-induced up-regulation of p21cip-1/WAF-1 in T cells was p53-independent. T cells deficient in p21cip-1/WAF-1 were less susceptible to CD95-induced apoptosis. We conclude that in T cells, ligation of CD95 and activation of caspases cause the induction of p21cip-1/WAF-1, which acts to promote cell death.

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Development of Inflammatory Angiogenesis by Local Stimulation of Fas In Vivo

Cited by 118 publications

References 21 publications

CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications

CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications

Apoptotic cues from the extracellular matrix: regulators of angiogenesis

CD95/Fas Signaling in T Lymphocytes Induces the Cell Cycle Control Protein p21cip-1/WAF-1, Which Promotes Apoptosis

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