Abstract
Imbalance in the network of soluble mediators may play a pivotal role in the pathogenesis of Kaposi's sarcoma (KS) a multifocal lesion characterized by a prominent angiogenesis. We demonstrated that KS cells grown in vitro produced and in part released platelet activating factor (PAF), a lipid mediator of inflammation and cell-to-cell communication. ILI, TNF and thrombin enhanced the synthesis of PAF. PAF receptor mRNA and specific, high affinity binding site for PAF were present in KS cells. Nanomolar concentration of PAF stimulated the chemotaxis and chemokinesis of KS cells, endothelial cells (EC) and vascular smooth muscle cells. The migration response to PAF was inhibited by WEB 2170, a PAF receptor antagonist. Since PAF activates EC we examined the potential role of PAF as an instrumental mediator of angiogenesis associated with KS. Conditioned medium (CM) from KS cells (KS-CM) or KS cells themselves induced angiogenesis and macrophage recruitment in Matrigel model. These effects were inhibited by treating mice with WEB 2170. The action of PAF was amplified by expression of other angiogenic factors and chemokines: these included basic and acidic FGF, PIGF, VEGF and its specific receptor flk-1 , HGF, KC, and MIP2. Treatment with WEB 2170 abolished the expression of these transcripts within Matrigel containing KS-CM. These results indicate that PAF may cooperate with other angiogenic molecules and chemokines in inducing vascular development, in KS.
Published Version
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