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 language | English |
|---|---|
| Pages (from-to) | 511-518 |
| Number of pages | 8 |
| Journal | Transplantation |
| Volume | 81 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 1 2006 |
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Keywords
- Endothelial cells
- Inflammation
- Islet transplantation
- Pancreatic islets
ASJC Scopus subject areas
- Transplantation
- Immunology
Cite this
Platelet-activating factor synthesis and response on pancreatic islet endothelial cells : Relevance for islet transplantation. / Biancone, Luigi; Cantaluppi, Vincenzo; Romanazzi, Giuseppe Mauriello; Russo, Simona; Figliolini, Federico; Beltramo, Silvia; Scalabrino, Elisa; Deregibus, Maria Chiara; Romagnoli, Renata; Franchello, Alessandro; Salizzoni, Mauro; Perin, Paolo Cavallo; Ricordi, Camillo; Segoloni, Giuseppe Paolo; Camussi, Giovanni.
In: Transplantation, Vol. 81, No. 4, 01.02.2006, p. 511-518.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Platelet-activating factor synthesis and response on pancreatic islet endothelial cells
T2 - Relevance for islet transplantation
AU - Biancone, Luigi
AU - Cantaluppi, Vincenzo
AU - Romanazzi, Giuseppe Mauriello
AU - Russo, Simona
AU - Figliolini, Federico
AU - Beltramo, Silvia
AU - Scalabrino, Elisa
AU - Deregibus, Maria Chiara
AU - Romagnoli, Renata
AU - Franchello, Alessandro
AU - Salizzoni, Mauro
AU - Perin, Paolo Cavallo
AU - Ricordi, Camillo
AU - Segoloni, Giuseppe Paolo
AU - Camussi, Giovanni
PY - 2006/2/1
Y1 - 2006/2/1
N2 - 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.
AB - 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.
KW - Endothelial cells
KW - Inflammation
KW - Islet transplantation
KW - Pancreatic islets
UR - http://www.scopus.com/inward/record.url?scp=33644630005&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644630005&partnerID=8YFLogxK
U2 - 10.1097/01.tp.0000200306.51689.f2
DO - 10.1097/01.tp.0000200306.51689.f2
M3 - Article
C2 - 16495796
AN - SCOPUS:33644630005
VL - 81
SP - 511
EP - 518
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 4
ER -