Transendothelial migration leads to protection from starvation-induced apoptosis in CD34+CD14+ circulating precursors: evidence for PECAM-1 involvement through Akt/PKB activation.
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.
Ferrero
Elisabetta
E
Laboratory of Tumor Immunology, the Human Virology Unit, Dibit, Italy.
Belloni
Daniela
D
Contini
Paola
P
Foglieni
Chiara
C
Ferrero
Maria Elena
ME
Fabbri
Monica
M
Poggi
Alessandro
A
Zocchi
Maria Raffaella
MR
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
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