Platelet-activating factor synthesis and response on pancreatic islet endothelial cells: Relevance for islet transplantation

Luigi Biancone, Vincenzo Cantaluppi, Giuseppe Mauriello Romanazzi, Simona Russo, Federico Figliolini, Silvia Beltramo, Elisa Scalabrino, Maria Chiara Deregibus, Renata Romagnoli, Alessandro Franchello, Mauro Salizzoni, Paolo Cavallo Perin, Camilla Ricordi, Giuseppe Paolo Segoloni, Giovanni Camussi

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background. Recent data suggest that donor intraislet endothelial cells may survive islet transplantation and participate to the events that influence islet engraftment. However, the mechanisms that regulate islet endothelial behavior in this setting are poorly known. Methods. We obtained immortalized human (hIECs) and mouse (mIECs) islet endothelial cells by transfection with SV40-T-large antigen and studied the synthesis and response to Platelet-activating factor (PAF), a multipotent phospholipid that acts as endothelial mediator of both inflammation and angiogenesis. Results. HIECs showed typical endothelial markers such as expression of vWF, CD31, and CD105, uptake of acetylated-LDL and binding to ULE-A lectin. Moreover, they expressed nestin, the PAF-receptor and possess surface fenestrations and in vitro angiogenic ability of forming tubular structures on Matrigel. Likewise, mIECs showed expression of vWF, CD31, nestin, PAF-receptor and CD105, and uptake of acetylated-LDL. HIECs and mIECs rapidly produced PAF under stimulation with thrombin in a dose-dependent way. Exogenous PAF or thrombin-induced PAF synthesis increased leukocyte adhesion to hIECS and mIECs and cell motility of both endothelial cell lines. Moreover, PAF or thrombin-induced PAF synthesis accellerated in vitro formation of vessel-like tubular structures when hIECs are seeded on Matrigel. Notably, gene-microarray analysis detected up-regulation of β3 integrin gene on hIECs stimulated with PAF, that was confirmed at the protein level. Conclusions. Based on the novel development of immortalized islet endothelium, these results suggest that PAF may have a dual role that links inflammation to angiogenesis in the early events of islet transplantation.

Original languageEnglish (US)
Pages (from-to)511-518
Number of pages8
JournalTransplantation
Volume81
Issue number4
DOIs
StatePublished - Feb 1 2006

Keywords

  • Endothelial cells
  • Inflammation
  • Islet transplantation
  • Pancreatic islets

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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    Biancone, L., Cantaluppi, V., Romanazzi, G. M., Russo, S., Figliolini, F., Beltramo, S., Scalabrino, E., Deregibus, M. C., Romagnoli, R., Franchello, A., Salizzoni, M., Perin, P. C., Ricordi, C., Segoloni, G. P., & Camussi, G. (2006). Platelet-activating factor synthesis and response on pancreatic islet endothelial cells: Relevance for islet transplantation. Transplantation, 81(4), 511-518. https://doi.org/10.1097/01.tp.0000200306.51689.f2