title: Transendothelial migration leads to protection from starvation-induced apoptosis in CD34+CD14+ circulating precursors: evidence for PECAM-1 involvement through Akt/PKB activation.
abstract: In the present paper we show that transendothelial migration of a subset of CD14(+) circulating leukocytes, coexpressing the CD34 precursor marker, leads to protection from the apoptosis that follows growth factor(s) withdrawal. The resistance of this cell subset to starvation-induced programmed cell death, lasting from 48 to 96 hours, is accompanied by a rise of mitochondrial adenosine triphosphate (ATP), a high nicotinamide adenine dinucleotide (NAD)/reduced nicotinamide adenine dinucleotide (NADH) ratio, and by the up-regulation of expression of the antiapoptotic proteins Bcl-2 and Bcl-X, together with an increase in the cytoplasmic, inactive, form of Bax. This suggests that protection from apoptosis is due to the preservation of mitochondrial function(s). Interestingly, ligation of the platelet endothelial cell adhesion molecule-1 (PECAM-1), which drives CD14(+)CD34(+) transendothelial migration, leads to an increase in Bcl-2 A1 and Bcl-X intracellular content, and to protection from starvation-induced apoptosis. This event is dependent on the engagement of phosphatidylinositol-3 kinase and activation of Akt/PKB that is known to contribute to Bcl-2 and Bcl-X induction. These data point to a critical role of endothelium in preventing the apoptotic program triggered by starvation, possibly inducing a prolonged survival of antigen presenting cell precursors, in order to allow recirculation of these cells and localization to the site of priming of T lymphocytes.
authors.affiliation: Laboratory of Tumor Immunology, the Human Virology Unit, Dibit, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferrero
authors.forename: Daniela
authors.initials: D
authors.lastname: Belloni
authors.forename: Paola
authors.initials: P
authors.lastname: Contini
authors.forename: Chiara
authors.initials: C
authors.lastname: Foglieni
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Ferrero
authors.forename: Monica
authors.initials: M
authors.lastname: Fabbri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poggi
authors.forename: Maria Raffaella
authors.initials: MR
authors.lastname: Zocchi
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D018952:Antigens, CD34; D017209:Apoptosis / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000276:immunology; D018950:Lipopolysaccharide Receptors; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000032:analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013217:Starvation; D014471:Umbilical Veins; D015854:Up-Regulation; D051020:bcl-X Protein
chemical_list: D018952:Antigens, CD34; C494811:BCL2L1 protein, human; D018950:Lipopolysaccharide Receptors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D009243:NAD; D000255:Adenosine Triphosphate; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt