title: Identification of CD300a as a new hypoxia-inducible gene and a regulator of CCL20 and VEGF production by human monocytes and macrophages.
abstract: Peripheral blood monocytes are recruited to inflammatory and tumor lesions where they undergo terminal differentiation into macrophages. Monocytes/macrophages integrate stimulatory and inhibitory signals present in the pathologic microenvironment through a defined repertoire of cell surface receptors, and deregulated expression of these molecules may result in amplification of inflammation or establishment of immune escape mechanisms. Characterization of the expression and function of these receptors is required for a better understanding of the regulation of monocyte/macrophage activity at pathologic sites. Hypoxia is a common feature of many pathological situations and an important regulator of monocyte/macrophage pro-inflammatory responses. In this study, we identify the leukocyte membrane antigen, CD300a, a member of the CD300 superfamily of immunoregulatory receptors, as a new hypoxia-inducible gene in primary human monocytes and monocyte-derived macrophages. CD300a mRNA up-regulation by hypoxia was rapid and reversible, paralleled by increased surface protein expression, and mediated by hypoxia-inducible factor-1α. CD300a induction was also triggered by the hypoxia-mimetic agent, desferrioxamine. CD300a exhibited both activating and inhibitory potential, differentially regulating CCL20 and vascular endothelial growth factor pro-inflammatory cytokine production by monocytes/macrophages upon triggering by an agonist Ab. These results suggest that CD300a induction by the hypoxic environment represents a mechanism of regulation of monocyte/macrophage pro-inflammatory responses at pathologic sites.
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Raggi
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Blengio
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Eva
authors.affiliation: IRCSS AOU San Martino-IST, Genova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Varesio
authors.affiliation: Laboratory of Molecular Biology, Istituto Giannina Gaslini, Genova, Italy mariacarlabosco@ospedale-gaslini.ge.it.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Bosco
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D054418:Chemokine CCL20 / Q000096:biosynthesis*; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism*; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D011971:Receptors, Immunologic / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; C515070:CD300A protein, human; D054418:Chemokine CCL20; D007502:Iron Chelating Agents; D011971:Receptors, Immunologic; D042461:Vascular Endothelial Growth Factor A
keywords: Hypoxia; immunoregulatory receptors; inflammation; monocytes/macrophages