Platelet-Activating Factor Synthesis and Response on Pancreatic Islet Endothelial Cells: Relevance for Islet Transplantation

Biancone, Luigi; Cantaluppi, Vincenzo; Romanazzi, Gianfranco; Russo, Simona; Figliolini, Federico; Beltramo, Silvia; Scalabrino, Elisa; Deregibus, Maria Chiara; Romagnoli, Renato; Franchello, A; Salizzoni, Mauro; Perin, Paolo Cavallo; Ricordi, Camillo; Segoloni, Giuseppe; Camussi, Giovanni

doi:10.1097/01.tp.0000200306.51689.f2

Cited by 10 publications

(10 citation statements)

References 42 publications

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“…The effects of coagulation on inflammation after Tx have recently been reviewed [34]. In addition, activated portal endothelial cells produce platelet-activating factor, which is a potent neutrophil chemoattractant [35]. Furthermore, the complement activation products, soluble C3a and C5a, serve as highly potent chemoattractractants for neutrophils and macrophages, thereby catalyzing the inflammatory reaction [6].…”

Section: Infiltration Of Inflammatory Cells: Neutrophilic Granulocytementioning

confidence: 99%

Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies

Windt

Bottino

Casu

et al. 2007

Xenotransplantation

159

109

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Islets isolated from multiple pancreas donors are often necessary to achieve euglycemia in type 1 diabetic patients treated by islet allotransplantation. This increases the burden on the limited pool of donor organs. After infusion into the portal vein, a substantial percentage of islets are lost in the immediate post-transplant period through an inflammatory response termed the instant blood-mediated inflammatory reaction (IBMIR). IBMIR is equally, if not more of a problem after islet xenotransplantation, e.g., using pig islets in non-human primates. Coagulation, platelet aggregation, complement activation, and neutrophil and monocyte infiltration play roles in this reaction. IBMIR is potentially triggered by islet surface molecules, such as tissue factor and collagen residues that are normally not in direct contact with the blood. Also, stress during the islet isolation process results in the expression and production of several inflammatory mediators by the islets themselves. The potential mechanisms involved in this rapid graft loss and treatment options to reduce this loss are reviewed. Preventive strategies for IBMIR can include systemic treatment of the recipient, pre-conditioning of the isolated islets, or, in the case of xenotransplantation, genetic modification of the organ-source pig. Pre-conditioning of islets in culture by exposure to anti-inflammatory agents or by genetic modification harbors fewer risks of systemic complications in the recipient. The future of clinical islet transplantation will, at least in part, depend on the success of efforts made to reduce rapid graft loss, and thus allow islet transplantation to become a more efficient therapy by the use of single donors.

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Section: Infiltration Of Inflammatory Cells: Neutrophilic Granulocytementioning

confidence: 99%

Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies

Windt

Bottino

Casu

et al. 2007

Xenotransplantation

159

109

View full text Add to dashboard Cite

show abstract

“…Although progress has been made in the imaging of transplanted islets, which can be labeled before transplantation (8–11,17,18), the imaging of the native islets within an entire, intact pancreas still raises significant challenges. This is because of the small size of pancreatic islets, their scattering within the pancreas, their poor contrast relative to that of the surrounding tissues, and the deep position of the pancreas within the abdomen.…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Magnetic Resonance Imaging Quantitatively Detects Individual Pancreatic Islets

et al. 2011

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OBJECTIVEWe studied whether manganese-enhanced high-field magnetic resonance (MR) imaging (MEHFMRI) could quantitatively detect individual islets in situ and in vivo and evaluate changes in a model of experimental diabetes.RESEARCH DESIGN AND METHODSWhole pancreata from untreated (n = 3), MnCl2 and glucose-injected mice (n = 6), and mice injected with either streptozotocin (STZ; n = 4) or citrate buffer (n = 4) were imaged ex vivo for unambiguous evaluation of islets. Exteriorized pancreata of MnCl2 and glucose-injected mice (n = 6) were imaged in vivo to directly visualize the gland and minimize movements. In all cases, MR images were acquired in a 14.1 Tesla scanner and correlated with the corresponding (immuno)histological sections.RESULTSIn ex vivo experiments, MEHFMRI distinguished different pancreatic tissues and evaluated the relative abundance of islets in the pancreata of normoglycemic mice. MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice. However, in the latter measurements the loss of β-cells was undervalued under the conditions tested. The experiments on the externalized pancreata confirmed that MEHFMRI could visualize native individual islets in living, anesthetized mice.CONCLUSIONSData show that MEHFMRI quantitatively visualizes individual islets in the intact mouse pancreas, both ex vivo and in vivo.

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“…However, islet endothelial cells contain a cytokine-inducible NO synthase that may generate NO in concentrations that lyse rodent b-cells [93]. Islet endothelial cells could also express components of the innate immune systems, such as Toll-like receptor 4 [94], that have been implicated in both the pathogenesis of Type 1 and Type 2 diabetes [95,96], as well as other receptors that can mediate tissue inflammation such as those for platelet activating factor [97]. Interestingly, islet endothelial cells seem to be very susceptible to hyperglycemia, which may cause a rapid loss of islet vasculature due to apoptosis during manifest diabetes [98].…”

Section: Changes In Islet Endothelial Cells During Islet Diseasementioning

confidence: 99%

Vascular niche of pancreatic islets

Olerud

Johansson

Carlsson

2009

Expert Review of Endocrinology & Metabolism

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Pancreatic islets are highly vascularized micro-organs. Approximately 10% of an islet consists of blood vessels. The induction and maintenance of the islet vascular system depend on VEGF secreted from b-cells. VEGF is also critical for the phenotype of the islet vasculature by induction of a vast number of fenestrae. The islet vasculature serves the role of supplying the endocrine cells with oxygen and nutrients, but may also be important for proper glucose sensing of the cells, for paracrine support of endocrine function and growth, and for drainage of metabolites and secreted islet hormones into the systemic circulation. Emerging evidence suggests an important role of islet endothelial cells to maintain b-cell function and growth by secretion of molecules such as hepatocyte growth factor, thrombospondin-1 and laminins, thereby forming a vascular niche for the endocrine cells. Keywords: diabetes • endothelial cell • hepatocyte growth factor • islet transplantation • laminin • pancreatic islets • thrombospondin-1 • vascular endothelial growth factor Vascular niche of pancreatic islets Expert Rev.

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Platelet-Activating Factor Synthesis and Response on Pancreatic Islet Endothelial Cells: Relevance for Islet Transplantation

Abstract: 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.

Cited by 10 publications

References 42 publications

Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies

Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies

High-Resolution Magnetic Resonance Imaging Quantitatively Detects Individual Pancreatic Islets

Vascular niche of pancreatic islets

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