Accuri C6 Flow Cytometer System
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0608345

Received for publication June 10, 2008.
Revised February 20, 2009.
Accepted for publication February 28, 2009.

Article

Coregulation in human leukocytes of the long pentraxin PTX3 and TSG-6

Virginia Maina *{dagger}, Alessia Cotena *{dagger}, Andrea Doni *, Manuela Nebuloni {ddagger}, Fabio Pasqualini *, Caroline M. Milner {sect}, Anthony J. Day {sect}, Alberto Mantovani *{dagger}, and Cecilia Garlanda *@

*Research Laboratory in Immunology and Inflammation, Istituto Clinico Humanitas (ICH), Rozzano, Milan, Italy;{dagger}Institute of General Pathology, University of Milan, Italy;{ddagger}Pathology Unit, L. Sacco Department of Clinical Sciences, University of Milan, Milan, Italy; and{sect}Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom

@ To whom correspondence should be addressed. E-mail: cecilia.garlanda{at}humanitas.it.


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Abstract

The prototypic long PTX3 is a multifunctional protein involved in innate resistance to pathogens and in controlling inflammation. TSG-6 is a hyaluronan-binding protein that is involved in ECM remodeling and has anti-inflammatory and chondroprotective functions. PTX3 and TSG-6 are coregulated by growth differentiation factor-9 in granulosa cells, where they are produced during the periovulatory period and play essential roles in the incorporation of hyaluronan into the ECM during cumulus expansion. The present study was designed to assess whether PTX3 and TSG-6 are coregulated in leukocytes, in particular, in phagocytes and DC. Monocytes, macrophages, and myeloid DC were found to produce high levels of TSG-6 and PTX3 in response to proinflammatory mediators (LPS or cytokines). Unstimulated neutrophil polymorphonuclear granulocytes expressed high levels of TSG-6 mRNA, but not PTX3 transcript, and stored both proteins in granules. In contrast, endothelial cells expressed substantial amounts of PTX3 mRNA and low levels of TSG-6 transcript under the conditions tested. Anti-inflammatory cytokines, such as IL-4, dampened LPS-induced TSG-6 and PTX3 expression. Divergent effects were observed with IL-10, which synergizes with TLR-mediated PTX3 induction but inhibits LPS-induced TSG-6 transcription. Immunohistochemical analysis confirms the colocalization of the two proteins in inflammatory infiltrates and in endothelial cells of inflamed tissues. Thus, here we show that myelomonocytic cells and MoDC are a major source of TSG-6 and that PTX3 and TSG-6 are coregulated under most of the conditions tested. The coordinated expression of PTX3 and TSG-6 may play a role in ECM remodeling at sites of inflammation.

Key Words: extracellular matrix • inflammation • acute-phase reactants • dendritic cells • neutrophils