Plasminogen activator inhibitor 2: a new plasma and cellular marker for leukemias with a monocytic component

Scherrer, Anne Paule Marie; Kruithof, E.K.O.; Grob, J. P.

doi:10.1016/0268-9499(90)90157-f

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“…In support of the role of PAI-2 in cell death, PAI-2 is expressed in vivo in skin (65) in a zone associated with keratinocyte differentiation and apoptosis. Tumor cells have also been found to synthesize PAI-2 (66,67), and transformation by ras and src oncogenes has been shown to induce PAI-2 expression in vitro (68). Given the effect of PAI-2 on cell survival, acquisition of PAI-2 expression by tumor cells may reduce their susceptibility to TNF-mediated apoptosis and thereby allow a selective survival advantage to these tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Plasminogen Activator Inhibitor Type 2 Inhibits Tumor Necrosis Factor α-induced Apoptosis

Dickinson¹,

Bates²,

Fèrrante³

et al. 1995

Journal of Biological Chemistry

214

229

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Plasminogen activator inhibitor type 2 (PAI-2) is a serine proteinase inhibitor or serpin that is a major product of macrophages in response to endotoxin and inflammatory cytokines. We have explored the role of PAI-2 in apoptotic cell death initiated by tumor necrosis factor alpha (TNF). HeLa cells stably transfected with PAI-2 cDNA were protected from TNF-induced apoptosis, whereas cells transfected with antisense PAI-2 cDNA, a control gene, or the plasmid vector alone remained susceptible. The level of PAI-2 expressed by different HeLa cell clones was inversely correlated with their sensitivity to TNF. Loss of TNF sensitivity was not a result of loss of TNF receptor binding. In contrast, PAI-2 expression did not confer protection against apoptosis induced by ultraviolet or ionizing radiation. The serine proteinase urokinase-type plasminogen activator was not demonstrated to be the target of PAI-2 action. The P1-Arg amino acid residue of PAI-2 was determined to be required for protection, because cells expressing PAI-2 with an Ala in this position were not protected from TNF-mediated cell death. The results suggest that intracellular PAI-2 might be an important factor in regulating cell death in TNF-mediated inflammatory processes through inhibition of a proteinase involved in TNF-induced apoptosis.

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Section: Discussionmentioning

confidence: 99%