CD300a is a new hypoxia-inducible gene and a regulator of proinflammatory cytokine production in human monocytes and macrophages
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1
G.Gaslini Institute, Department of Experimental and Clinical Research, Italy
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 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 effects of pathologic stimuli on the expression and function of these receptors may, thus, contribute to our understanding of monocytic lineage cell functions in diseased tissues. A common feature at pathologic sites and an important regulator of monocyte/macrophage proinflammatory functions is represented by low partial oxygen pressure (hypoxia). We recently identified by gene expression profiling the leukocyte membrane antigen, CD300a, a member of the Ig-like CD300 superfamily of imunoreceptors, as a new hypoxia-inducible gene in primary human monocytes. In this study, we demonstrate that CD300a mRNA and surface protein are upregulated by hypoxia and the hypoxia-mimetic agent, desferrioxamine, in both monocytes and monocyte-derived macrophages. Stimulatory effects are reversible, being counteracted by cell reoxygenation or addition of iron sulfate. Interestingly, CD300a ligation by an agonist Ab delivers both inhibitory and activating signals in these cells, differentially affecting the production of the chemotactic and proangiogenic cytokines, CCL20 and VEGF, driven by hypoxia and desferrioxamine. These findings point to a role for this molecule in the regulation of monocyte/macrophage inflammatory and angiogenic activity at hypoxic sites, with potential implications for inflammatory diseases and cancer pathogenesis.
Keywords:
monocytes/macrophages,
Hypoxia-Inducible Factor 1,
immunoregulatory receptors,
Inflammation,
Gene Expression Regulation
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Raggi
F,
Blengio
F,
Varesio
L and
Bosco
M
(2013). CD300a is a new hypoxia-inducible gene and a regulator of proinflammatory cytokine production in human monocytes and macrophages.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00980
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Received:
28 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Federica Raggi, G.Gaslini Institute, Department of Experimental and Clinical Research, Genova, Italy, federicaraggi@gaslini.org
Dr. Maria Carla Bosco, G.Gaslini Institute, Department of Experimental and Clinical Research, Genova, Italy, mariacarlabosco@ospedale-gaslini.ge.it