Cardiovascular Research Advance Access [Accepted Manuscript] published online on August 28, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn234
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Secreted phospholipase A2 type IIA as a mediator connecting innate and adaptive immunity. New role in atherosclerosis
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas/Universidad de Valladolid. 47005-Valladolid, Spain
Correspondence: Dr. ML. Nieto, Instituto de Biología y Genética Molecular. Facultad de Medicina, C/ Sanz y Fores s/n. 47003-Valladolid, SPAIN, Telephone: 34-983-184836, FAX: 34-983-184800, e-mail: mlnieto{at}ibgm.uva.es
Aims: Human atherosclerotic plaques express markers of macrophage/dendritic cells as well as high levels of inflammatory proteins such as secreted phospholipase A2 type IIA (sPLA2-IIA). To understand the cellular changes associated with the progress of atherosclerosis, the purpose of this study was to evaluate the role of sPLA2-IIA in mediating monocyte recruitment and differentiation into antigen-presenting cells.
Methods and Results: The effect of sPLA2-IIA on monocyte differentiation was evaluated in human THP-1 cells, a cellular line widely used as a model for monocyte-macrophage differentiation. Changes in functional processes, morphology and expression of antigens, characteristic of differentiated cells, were monitored over a 1- to 3-day period. sPLA2-IIA inhibited CD14 expression in a time- and concentration-dependent manner and up-regulated DC-SING (dendritic cell-specific ICAM-3 grabbing nonintegrin) levels at the cell surface, findings that were the same for human monocytes. In addition, sPLA2-IIA-differentiated cells showed a dendritic cell phenotype characterized by the generation of fine dendritic protrusions and an increase in surface markers such as CD40, CD83, CD54, CD61 and CD62L. Furthermore, cell adhesion, migration, endocytic activity and allogeneic T cell proliferation capacity were markedly increased after sPLA2-IIA treatment.
Conclusions: -sPLA2-IIA induces differentiation of mononuclear cells and increases their adhesive and migratory capability, which suggests a novel function for sPLA2-IIA as a mediator connecting innate and adaptive immunity. These findings may provide insight into the immuno-inflammatory processes occurring in atherosclerosis, helping us to understand the cellular changes associated with the development of atherosclerosis.
KEYWORDS atherosclerosis; dendritic cells; macrophages; inflammation; sPLA2-IIA
Time for primary review: 23 Days
* Elvira Ibeas and Lucia Fuentes contributed equally to this work
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Cardiovasc Res 2009 81: 9-10.
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