title: Inflammatory environment and oxidized LDL convert circulating human proangiogenic cells into functional antigen-presenting cells.
abstract: The function of human circulating PACs has been described extensively. However, little focus has been placed on understanding how these cells differ in their functions in the presence of microenvironments mimicking vascular inflammation. We hypothesized that exposure to proinflammatory cytokines or the oxLDL, an autoantigen abundant in advanced atherosclerotic plaques, converts PACs into immune-modulating/proinflammatory cells. Hence, we examined the effect of oxLDL and inflammatory stimuli on their phenotype by use of a functional genomics model based on secretome and whole genome transcriptome profiling. PACs obtained from culturing a PBMC fraction in angiogenic medium were primed with DC differentiation cytokines and then exposed to proinflammatory cytokines or oxLDL. Under these conditions, PACs converted into APCs, expressed maturation markers CD80 and CD83, and showed an increased up-regulation of CD86. APCcy and APCox induced a robust T cell BrdU incorporation. Despite a similar ability to induce lymphocyte proliferation, APCcy and APCox differed for the secretory pathway and mRNA expression. Analysis of the differentially expressed genes identified 4 gene "clusters," showing reciprocal modulation in APCcy vs. APCox, justifying, according to functional genomics analyses, a different putative function of the cells in antigen processing. Together, these data show that treatment with inflammatory cytokines or oxLDL converts human PAC phenotypes and functions into that of APCs with similar lymphocyte-activating ability but distinct maturation degree and paracrine functions.
authors.affiliation: *Unità di Ingegneria Tissutale Cardiovascolare and Unità di Immunologia e Genomica Funzionale, Centro Cardiologico Monzino, Istituto Di Ricovero e Cura a Carattere Scientifico, Milan, Italy maurizio.pesce@ccfm.it cristina.vinci@ccfm.it.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Vinci
authors.affiliation: *Unità di Ingegneria Tissutale Cardiovascolare and Unità di Immunologia e Genomica Funzionale, Centro Cardiologico Monzino, Istituto Di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Piacentini
authors.affiliation: *Unità di Ingegneria Tissutale Cardiovascolare and Unità di Immunologia e Genomica Funzionale, Centro Cardiologico Monzino, Istituto Di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Chiesa
authors.affiliation: *Unità di Ingegneria Tissutale Cardiovascolare and Unità di Immunologia e Genomica Funzionale, Centro Cardiologico Monzino, Istituto Di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Saporiti
authors.affiliation: *Unità di Ingegneria Tissutale Cardiovascolare and Unità di Immunologia e Genomica Funzionale, Centro Cardiologico Monzino, Istituto Di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Gualtiero I
authors.initials: GI
authors.lastname: Colombo
authors.affiliation: *Unità di Ingegneria Tissutale Cardiovascolare and Unità di Immunologia e Genomica Funzionale, Centro Cardiologico Monzino, Istituto Di Ricovero e Cura a Carattere Scientifico, Milan, Italy maurizio.pesce@ccfm.it cristina.vinci@ccfm.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pesce
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D023281:Genomics; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D008077:Lipoproteins, LDL; D008934:Mitogens; C099252:oxidized low density lipoprotein
keywords: Ox-LDL; gene expression profiling