The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens

Baruah, Paramita; Propato, Antonella; Dumitriu, Ingrid E.; Rovere‐Querini, Patrizia; Russo, Vincenzo; Fontana, Raffaella; Accapezzato, Daniele; Peri, Giuseppe; Mantovani, Alberto; Barnaba, Vincenzo; Manfredi, Angelo A.

doi:10.1182/blood-2005-03-1112

Cited by 93 publications

(82 citation statements)

References 69 publications

(119 reference statements)

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“…The puzzle of how the pentraxins execute inflammatory anti-microbial responses, while at the same time silencing clonal expansion of autoreactive lymphocytes, has been resolved by new data supplied by Rovere and Baruah with colleagues. These data confirm a dual role for pentraxin 3 in reactions of innate immunity (35,4).…”

Section: Pentraxin 3 and Apoptotic Cellssupporting

confidence: 74%

Essential PTX3 Biology (not only) for Cardiologists and Cardiac Surgeons

Kuneš

Lonský

Mandak

et al. 2007

Acta Med. (Hradec Kralove, Czech Repub.)

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Summary: Inflammation has been recognized to form an integral part of the atherosclerotic process. Much consideration has been given lately to the role played in atherogenesis by C-reactive protein (CRP). Although not accepted unequivocally, CRP appears to be not only a marker, but also an active mediator of the atherosclerotic process. Pentraxin 3 (PTX3) is a newly identified acute phase reactant which shares some structural and some functional properties with CRP. On the other hand, pentraxin 3 displays unique biological properties of its own, including a possible role in the pathogenesis of cardiovascular diseases and in processes accompanying the natural evolution of surgical wounds. This review article discusses recent information concerning basic pentraxin 3 biology in inflammation and in innate immunity reactions as viewed by a cardiologist in the context of acute coronary events and by a surgeon in patients struck with multiple wounds who are at the same time menaced by bacterial infections.

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Section: Pentraxin 3 and Apoptotic Cellssupporting

confidence: 74%

Essential PTX3 Biology (not only) for Cardiologists and Cardiac Surgeons

Kuneš

Lonský

Mandak

et al. 2007

Acta Med. (Hradec Kralove, Czech Repub.)

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“…Therefore, we have started in vitro experiments to investigate the possible mechanism, how necrotic but not apoptotic tumor cells impair CD8 ϩ T cell responses. Uric acid (45,46), heat shock proteins (47,48), pentraxins (49,50), and phosphatidyl-serine expression on apoptotic cells (51) have been suggested as possible links between abrupt cell death and immune responses generation (4). We have not been able to analyze these factors in our experimental set up, however, we have shown that anti-CD40 treatment reversed the impairment seen in mice with necrotic tumors.…”

Section: Discussionmentioning

confidence: 99%

Necrotic Tumor Cell Death In Vivo Impairs Tumor-Specific Immune Responses

Gamrekelashvili¹,

Krüger²,

Wasielewski

et al. 2007

The Journal of Immunology

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The manner in which cells die is believed to have a major impact on the nature of immune responses to their released Ags. In this study, we present the first direct analysis of tumor-specific immune responses to in vivo occurring tumor cell death through apoptosis or necrosis. Mice bearing thymidine kinase-transfected tumors were treated either with ganciclovir to induce tumor cell apoptosis in vivo or a vascular targeting agent, ZD6126, to induce tumor cell necrosis in vivo. In contrast to tumor apoptosis, induction of necrosis reduced the frequency and impaired the function of tumor-specific CD8+ T cells. Adoptive transfer of lymphocytes from mice with apoptotic tumors into tumor-challenged mice resulted in a significant tumor protection, which was absent when splenocytes were transferred from mice with necrotic tumors. Anti-CD40 treatment reversed impaired Ag-specific CD8+ T cell responses in these mice. These observations have not only fundamental importance for the development of immunotherapy protocols but also help to understand the underlying mechanism of in vivo immune responses to tumor cell death.

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“…Previous studies on Ptx3 Ϫ/Ϫ mice suggested that PTX3 acts as a central "node" in cumulus matrix organization by establishing multivalent contacts to the HA-binding protein tumor necrosis factor-stimulated gene-6 protein (TSG-6) (9,14,15) and the serum protein inter-␣-inhibitor (16). PTX3 also plays a role in regulating the scavenger activity of macrophages and dendritic cells by direct binding to apoptotic cells (17)(18)(19)(20).…”

mentioning

confidence: 99%

Structural Characterization of PTX3 Disulfide Bond Network and Its Multimeric Status in Cumulus Matrix Organization

Inforzato

Rivieccio²,

Morreale

et al. 2008

Journal of Biological Chemistry

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119

129

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PTX3 is an acute phase glycoprotein that plays key roles in resistance to certain pathogens and in female fertility. PTX3 exerts its functions by interacting with a number of structurally unrelated molecules, a capacity that is likely to rely on its complex multimeric structure stabilized by interchain disulfide bonds. In this study, PAGE analyses performed under both native and denaturing conditions indicated that human recombinant PTX3 is mainly composed of covalently linked octamers. The network of disulfide bonds supporting this octameric assembly was resolved by mass spectrometry and Cys to Ser site-directed mutagenesis. Here we report that cysteine residues at positions 47, 49, and 103 in the N-terminal domain form three symmetric interchain disulfide bonds stabilizing four protein subunits in a tetrameric arrangement. Additional interchain disulfide bonds formed by the C-terminal domain cysteines Cys 317 and Cys 318 are responsible for linking the PTX3 tetramers into octamers. We also identified three intrachain disulfide bonds within the C-terminal domain that we used as structural constraints to build a new three-dimensional model for this domain. Previously it has been shown that PTX3 is a key component of the cumulus oophorus extracellular matrix, which forms around the oocyte prior to ovulation, because cumuli from PTX3 ؊/؊ mice show defective matrix organization. Recombinant PTX3 is able to restore the normal phenotype ex vivo in cumuli from PTX3 ؊/؊ mice. Here we demonstrate that PTX3 Cys to Ser mutants, mainly assembled into tetramers, exhibited wild type rescue activity, whereas a mutant, predominantly composed of dimers, had impaired functionality. These findings indicate that protein oligomerization is essential for PTX3 activity within the cumulus matrix and implicate PTX3 tetramers as the functional molecular units required for cumulus matrix organization and stabilization.

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The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens

Cited by 93 publications

References 69 publications

Essential PTX3 Biology (not only) for Cardiologists and Cardiac Surgeons

Essential PTX3 Biology (not only) for Cardiologists and Cardiac Surgeons

Necrotic Tumor Cell Death In Vivo Impairs Tumor-Specific Immune Responses

Structural Characterization of PTX3 Disulfide Bond Network and Its Multimeric Status in Cumulus Matrix Organization

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