Neutrophil degranulation, angiogenesis and wound healing are three important host responses during inflammation. In this thesis we studied how the immunocalin α1-acid glycoprotein (AGP), in its role of immunomodulatory acute phase protein, affected this processes. We studied bovine neutrophil degranulation within the frame of acute inflammation and we studied angiogenesis and wound healing on endothelial human primary cells. We found that AGP exhorts an important role downregulating both spontaneous and ZAS activated degranulation of secondary bovine neutrophil granules but not on primary granules, and it does it in a dose dependent way. Carbohydrate moiety was found to be critical since desialylated AGP did not have any effects on secondary granules exocytosis. When tested on endothelial cells AGP clearly inhibited Matrigel induced angiogenesis, and modulated endothelial cell adhesion in a biphasic way, inhibiting it at high concentrations. Migration into a wound was also inhibited by high concentrations of AGP in a reversible way. On the modified Boyden chambers AGP acted both as a chemokinetic and as a chemoattractant with results similar to those obtained when FBS was used as a chemoattractant. In our last set of experiments we tested human PMN adhesion to an endothelial monolayer, and we saw that AGP clearly inhibits fMLP/CytoB activated PMN’s to the monolayer whether this is LPS activated or not. Taken together this results support the hypothesis that AGP is heavily involved in the fine tuning of neutrophil activity in the inflammatory environment and endothelial cell behavior.
AGP REGULATES THE NEUTROPHIL AND ENDOTHELIAL CELL INFLAMMATORY RESPONSE / A. Miranda Ribera ; tutor: Fabrizio Ceciliani ; coordinatore: Fulvio Gandolfi. - Milano : Università degli studi di Milano. Universita' degli Studi di Milano, 2010 Dec 14. ((23. ciclo, Anno Accademico 2010.
|Titolo:||AGP REGULATES THE NEUTROPHIL AND ENDOTHELIAL CELL INFLAMMATORY RESPONSE|
|Supervisori e coordinatori interni:||GANDOLFI, FULVIO|
|Data di pubblicazione:||14-dic-2010|
|Parole Chiave:||Acute phase reaction ; granulocytes ; 1-acid glycoprotein ; exocytosis ; endothelial cells ; wound healing ; angiogenesis ; migration ; PMN adhesion|
|Settore Scientifico Disciplinare:||Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria|
|Citazione:||AGP REGULATES THE NEUTROPHIL AND ENDOTHELIAL CELL INFLAMMATORY RESPONSE / A. Miranda Ribera ; tutor: Fabrizio Ceciliani ; coordinatore: Fulvio Gandolfi. - Milano : Università degli studi di Milano. Universita' degli Studi di Milano, 2010 Dec 14. ((23. ciclo, Anno Accademico 2010.|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.13130/miranda-ribera-alba_phd2010-12-14|
|Appare nelle tipologie:||Tesi di dottorato|