title: Endothelial progenitor cells express PAF receptor and respond to PAF via Ca(2+)-dependent signaling.
abstract: Endothelial progenitor cell (EPC) therapy is a promising approach to promote angiogenesis and endothelial repair in patients with cardiovascular diseases (CVD). However, their release of proinflammatory mediators may compromise the therapeutic efficacy. Little is known about the role of Platelet-Activating Factor (PAF) in EPC functional response. Here, we investigated the expression of PAF receptor (PAF-R) in early EPC and the release of PAF under stimulation with factors involved in endothelial dysfunction. Results indicated that early EPC express the PAF-R and respond to PAF signaling via a transient increase of cytoplasmic Ca(2+) concentration. EPC release PAF in a time dependent manner upon stimulation with tumor necrosis factor-alpha (TNF-alpha) or high-glucose concentration with a peak at 30 min and 10 min (p<0.01 vs. control), respectively. PAF, starting at concentration of 50 ng/ml, exerted a detrimental effect on EPC number with a concomitant increase of p38 activity. Furthermore, both the reduction of early EPC number and the enhanced p38 activity induced by PAF were abolished by CV3988, a PAF receptor antagonist. These novel findings, revealing that early EPC respond to PAF signaling, unveil an inflammatory pathway that may play a crucial role in the outcome of cardiovascular cell therapy with EPC.
authors.affiliation: Department of Biochemistry and Biophysics, 1st School of Medicine, II University of Naples, 80138 Naples, Italy. marialuisa.balestrieri@unina2.it
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Balestrieri
authors.forename: Alfonso
authors.initials: A
authors.lastname: Giovane
authors.forename: Lara
authors.initials: L
authors.lastname: Milone
authors.forename: Luigi
authors.initials: L
authors.lastname: Servillo
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D002118:Calcium