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Obstetrics & Gynecology 2006;108:148-155
© 2006 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Plasma and Tissue Expression of the Long Pentraxin 3 During Normal Pregnancy and Preeclampsia

Patrizia Rovere-Querini, MD, PhD1, Simona Antonacci1, Giacomo Dell'Antonio, MD2, Anna Angeli, MD3, Giada Almirante, MD3, Elena Dal Cin2, Luca Valsecchi, MD3, Chiara Lanzani, MD4, Maria Grazia Sabbadini, MD1, Claudio Doglioni, MD2, Angelo A. Manfredi, MD1 and Maria Teresa Castiglioni, MD3

From the 1Clinical Immunology Unit, 2Division of Pathology, 3Division of Gynaecology and Obstetrics, and 4Division of Nephrology, H. San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milano, Italy.


   ABSTRACT
TOP
ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE: Cell death normally occurs during pregnancy and is critical during its common complication, preeclampsia. The long pentraxin 3 (PTX3) gene is generated in tissues that cope with excessive or deregulated cell death and inhibits the cross-presentation of cell-associated antigens. We examined whether PTX3 is expressed during pregnancy and possibly involved in the development of preeclampsia.

METHODS: Women with preeclampsia (n = 30), women with uncomplicated pregnancies (n = 66), age-matched healthy women (n = 50), women who developed acute bacterial infections (n = 20), and women with rheumatoid arthritis (n = 20) were studied. The concentrations of PTX3 were measured in the blood by a sandwich enzyme-linked immunosorbent assay (ELISA) and in placentas by immunohistochemistry. The concentrations of PTX3 and C-reactive protein in the various groups were compared by nonparametric tests (the Mann-Whitney U and the Kruskal-Wallis tests). The odds of developing preeclampsia were assessed using logistic regression.

RESULTS: PTX3 was expressed in amniotic epithelium and chorionic mesoderm, trophoblast terminal villi, and perivascular stroma in placentas from pregnancies of uncomplicated subjects. Circulating levels steadily rose during normal gestation and peaked during labor. Serum levels of PTX3 were strikingly higher in preeclampsia compared with normal control pregnancies (5.08 ± 1.34 and 0.59 ± 0.07 ng/mL, respectively, P < .001). Sites of higher expression in the placentas from preeclamptic patients include infarcts and fibrinoid zones.

CONCLUSION: Defects in the homeostatic response to cell death/remodeling events, revealed by enhanced levels of PTX3, could be implicated in preeclampsia.

LEVEL OF EVIDENCE: II-2

Infiltration of leukocytes and activation of endothelial cells and platelets are hallmarks of pregnancy. Inflammation could be due to extensive cell death in situ.1 Apoptosis takes place in the human placenta,2 with generation of blebs, postapoptotic debris, and membrane microparticles and release in the blood of cytokeratin fragments and fetal nucleic acids. Maternal immune responses against the fetus, which is genetically foreign, are effectively censored by a variety of mechanisms,3 including the failure of viable trophoblast cells to express human leukocyte antigen (HLA)-A, -B, and -D molecules.4 This, however, does not prevent the cross-presentation of fetal antigens by antigen-presenting cells that phagocytosed dying cells. Little is known about the events that prevent the cross-priming of maternal T cells against paternal alloantigens or antigens expressed in the developing embryo only.

Preeclampsia is a common disorder and a major cause of mortality and morbidities. On the maternal side, hypertension and proteinuria develop, which may or may not be associated with systemic involvement. On the fetal side, growth is restricted, the amniotic fluid reduced, and the supply of oxygen and nutrients impaired.1,4,5 Cell death is amplified during preeclampsia,6,7 with elevated levels of soluble Fas, shedding of apoptotic syncytiotrophoblasts, and raised concentrations of fetal DNA and cytokeratin in the maternal blood. Macroscopically, areas of ischemic villous necrosis and vaso-occlusive lesions are more represented in preeclampsia.13 An exaggerated maternal inflammatory response develops, with enhanced endothelial permeability and platelet aggregation. Cytokines, including tumor necrosis factor (TNF)-{alpha}, are expressed in the preeclamptic placenta.1,4,14 Tumor necrosis factor {alpha} at the membrane of apoptotic cells specifically favors the induction of cross-priming events.15

The long pentraxin 3 (PTX3) was first identified as a TNF-{alpha}–stimulated gene in fibroblasts16 and as an interleukin (IL)-1ß–inducible gene in endothelial cells.17 Elevated serum PTX3 levels have been described in some infectious and inflammatory conditions. Experimental models indicate a nonredundant role of PTX3 in immunity to fungi and in female fertility. Smooth muscle cells, adipocytes, mononuclear phagocytes, and dendritic cells produce PTX3 as well.

PTX3 binds to dying cells34 and restricts the cross-presentation of antigens derived from the processing of the dying cell, possibly limiting their immunogenicity.35 We hypothesized that PTX3 could reveal higher extents of cell death and tissue remodeling during preeclampsia, and therefore, that higher circulating levels of this protein could identify patients with preeclampsia.


   MATERIALS AND METHODS
TOP
ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Consecutive patients with preeclampsia (n = 30) and consecutive normotensive women with uncomplicated pregnancies (n = 66) were enrolled for this study in the Department of Obstetrics and Gynecology of the H. San Raffaele University Hospital, Milan, Italy, from March 2003 to February 2005. Gestational age, maternal weight, systolic and diastolic blood pressures, mode and age at delivery, and infant birth and placental weights were recorded. Comparisons were made between preeclamptic patients (n = 30) and those control pregnant women with a similar gestational age (controls, n = 37). The sample sizes were selected based on the results of a pilot study, using preeclamptic patients and pregnant women with a similar gestational age. We estimated that a 23-subject sample size for each group was the minimum requirement to obtain 90% power in evaluating differences between PTX3 concentrations. The observed power for our result is 92.5%. Moreover, we studied age-matched healthy women (healthy, n = 50), selected among the personnel of the Gynecology and the Clinical Immunology Unit of the same institution. Women who developed acute bacterial infections (pneumonia, pyelonephritis, n = 20) and women with active rheumatoid arthritis (n = 20) were also selected for this study. Patients with rheumatoid arthritis fulfilled the 1987 revised diagnostic criteria of the American Rheumatism Association/American College of Rheumatology (ARA/ACR). Disease activity was evaluated by means of the European League Against Rheumatism (EULAR) disease activity score 28 (DAS28). Disease activity score 28 is determined by a formula that takes into account the number of tender and swollen joints, erythrocyte sedimentation rate, and the patient visual analog scale for the pain. A single blood sample was derived by venipuncture from each subject at the time of enrollment in the study.

Preeclampsia was defined as a rise in blood pressure after 20 weeks of gestation to more than 140/90 mmHg on 2 or more occasions 4–6 hours apart in a previously normotensive woman, combined with urine excretion of protein greater than 300 mg every 24 hours. Most preeclamptic patients we studied (25/30) had severe preeclampsia, defined as systolic pressure greater than 160 mmHg and/or diastolic pressure greater than 110 mmHg and/or proteinuria greater than 5 g/L. Blood was derived from preeclamptic patients at the time of diagnosis. All patients provided written informed consent to this study. Gestational age was routinely confirmed by ultrasonography between gestational weeks 10 and 14. Patients were managed according to the guidelines proposed by the Società Lombarda di Ostetricia e Ginecologia, which are based on the recent standard accepted evidence and are summarized on the society's Web site (available at: http://www.slog.org; retrieved April 26, 2006). This study has been approved by the Institutional Review Board of the H. San Raffaele Scientific Institute (Comitato Etico dell'Istituto Scientifico Ospedale San Raffaele).

The concentrations of PTX3 were measured by a sandwich ELISA based on the MNB4 PTX3-specific monoclonal antibody and on biotinylated rabbit PTX3-specific polyclonal immunoglobulin (Ig)G (Sigma, St. Louis, MO). This assay is highly sensitive and specific; no cross-reactions were observed with other pentraxins or, in particular, with the C-reactive protein (CRP) or serum amyloid P component.36 C-reactive protein was assessed by nephelometry (BN II nephelometer; Dade Behring, Deerfield, IL).

Sections (3–4 µm thick) of paraffin-embedded placentas, fixed in neutral-buffered formalin, from 11 patients and 10 controls were analyzed. Samples were incubated in xylol and rehydrated and antigens retrieved (DakoCytomation, Carpinteria, CA). Endogenous peroxidase was quenched with 0.3% H2O2. Slides were blocked in 1:20 diluted serum and incubated with biotinylated PTX3-specific antibody MNB4 (40 µg/mL) before addition of peroxidase-conjugated streptavidin and 3,3'-diaminobenzidine (Novocastra Laboratories, Newcastle upon Tyne, UK). Sections were counterstained with hematoxylin. As a negative control, MNB4 was omitted and samples processed as above were incubated in the presence of peroxidase-conjugated streptavidin and 3,3'-diaminobenzidine only. Paraffinized skin sections from four patients with systemic small-vessel vasculitis and six healthy subjects were used as positive and negative controls for PTX3 expression, respectively.19 Two expert blinded pathologists (G.D.A. and C.D) independently evaluated randomly selected sections of placentas.

The characteristics of preeclamptic cases and controls were compared by using t tests for continuous variables. Nonnormally distributed continuous variables, including the concentrations of PTX3 and CRP, were compared with nonparametric tests (the Mann-Whitney U and the Kruskal-Wallis tests). The odds of developing preeclampsia were assessed using logistic regression. Analysis was performed with SPSS 11.0 for Macintosh (SPSS Inc, Chicago, IL).


   RESULTS
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ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
A specific signal was detectable in amniotic epithelium, chorionic mesoderm (Fig. 1A), and terminal villi (Fig. 1B), although with variable intensity in normal placentas. Endothelial cells were consistently negative. A variable signal was detectable in the perivascular stroma (Fig. 1C). PTX3 was detectable in the blood of pregnant women at different gestational ages. We observed a progressive elevation of the serum PTX3 levels during normal pregnancy (linear regression analysis R2 = 10.8, P = .007) (Fig. 1D). A further substantial elevation of PTX3 occurred at the time of labor, when programmed cell death is activated in concert with orchestrated extracellular matrix degradation37 (mean ± standard deviation at labor, 1.7 ± 0.7, versus between weeks 36 and 41, 0.63 ± 0.27 ng/mL, P < .05).


Figure 124
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  		Fig. 1. PTX3 expression during pregnancy. PTX3 expression was assessed on paraffined sections counterstained with hematoxylin by immunohistochemistry using the PTX3-specific antibody MNB4 (brown signal, A–C). Sections refer to amniotic epithelium and chorionic mesoderm (A), trophoblast terminal villi (B), and perivascular stroma (C). Original magnification: A and C x 200, B x 100. D. The scatter plot shows the relationship between the concentrations of PTX3 and gestational age at sampling in healthy pregnant women (filled diamonds, n = 66). Each subject was sampled once, and each symbol refers to a single subject.

Rovere-Querini. PTX3 and Preeclampsia. Obstet Gynecol 2006.

 

We then measured PTX3 in the serum of 30 consecutive patients with preeclampsia and in 37 controls with similar gestational age (controls) (gestational age at sampling, 34.17 ± 0.58, and 33.43 ± 0.71 weeks, respectively, P = .42). The characteristics of patients with preeclampsia and of pregnant controls are depicted in Tables 1 and 2. Levels of PTX3 were strikingly higher in patients with preeclampsia (Fig. 2A; 5.08 ± 1.34 versus 0.59 ± 0.07 ng/mL, P < .001). No significant difference was observed in the concentration of the related inflammatory pentraxin CRP (9.44 ± 2.67 versus 5.21 ± 1.1 µg/mL, P = .065) (Fig. 2B). Figure 2A also reports the circulating PTX3 levels in patients with active rheumatoid arthritis (n = 20, 1.68 ± 0.18 ng/mL) and microbial infections (n = 20, 0,47 ± 0.08 ng/mL) and in healthy nonpregnant women (n = 50, 0.48 ± 0.06 ng/mL). The results indicate that PTX3 elevation is selective, because circulating levels fail to increase even in patients with acute infection. Moreover, only a limited increase was detectable in patients with active inflammation due to relapsing rheumatoid arthritis. C-reactive protein was elevated in both active rheumatoid arthritis and infections (62.06 ± 10.3 and 109.9 ± 11.8 µg/mL, respectively) (Fig. 2B).


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  		Table 1. Patient Characteristics

 

Figure 224
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  		Fig. 2. Higher circulating levels of PTX3 in patients with preeclampsia. PTX3 (A) and C-reactive protein (B) were assessed in the peripheral blood of patients with preeclampsia (Preeclamptic, n = 30), normotensive healthy pregnant women with a similar gestational age (Controls, n = 37), women with active rheumatoid arthritis (Active RA, n = 20), women with pneumonia or pyelonephritis (Infection, n = 20), and nonpregnant healthy controls (Healthy, n = 20). ** Statistically significant differences (P < .001); ns, not significant.

Rovere-Querini. PTX3 and Preeclampsia. Obstet Gynecol 2006.

 


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  		Table 2. Clinical Features of Patients With Preeclampsia and Controls

 

Sites of higher PTX3 expression in the placentas from preeclamptic patients include infarctual areas (Fig. 3A, left), perivillous fibrinoid, basal plate Rohr fibrinoid zone, extravillous cytotrophoblast, and decidual cells (Figs. 3B and 3C). As in the placentas of healthy women, PTX3 was not expressed in vessel walls (Fig. 3D) but in the villar perivascular stroma (Figs. 3A, right, and 3D). The expression of PTX3 in the amniotic epithelium, chorionic mesoderm, and terminal villi of placentas from women with preeclampsia was focal and weak (Figs. 3E and 3F). No signal was detectable in the presence of the second-step reagent only (not shown).


Figure 324
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  		Fig. 3. PTX3 expression in preeclampsia. PTX3 expression was assessed on paraffined sections counterstained with hematoxylin by immunohistochemistry using the PTX3 specific antibody MNB4 (brown signal, A–F). Sections refer to infarctual areas (A), perivillous fibrinoid (B), basal plate, Rohr fibrinoid zone, extravillous cytotrophoblast, and decidual cells (C), perivascular stroma of stem villi (D), amniotic epithelium and chorionic mesoderm (E), and terminal villi (F). Original magnifications: C x 100; A, B, D, E, F x 200. G. The scatter plot shows the relationship between the concentrations of PTX3 and gestational age at sampling in patients with severe preeclampsia (filled circles, n = 25) and in patients with mild preeclampsia (white circles, n = 5). Each patient was sampled once, and each symbol refers to a single subject.

Rovere-Querini. PTX3 and Preeclampsia. Obstet Gynecol 2006.

 

Logistic regression analysis was used to evaluate the probability of developing preeclampsia based on the circulating levels of PTX3. The odds ratio associated with each increase of PTX3 was 14 (95% confidence interval 3.16–64.9). The values of PTX3 were higher in patients with severe preeclampsia (5.38 ± 1.3) than in patients with mild preeclampsia (1.3 ± 0.03). We failed to observe any correlation between circulating levels of PTX3 and gestational age at sampling in patients who developed preeclampsia (Fig. 3G). The substantially higher levels of PTX3, which are associated with the disease compared with normal controls (Fig. 2A), could mask the physiological increase in PTX3 levels during normal pregnancy.


   DISCUSSION
TOP
ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Most forms of tissue damage, infection, and neoplasia elicit a response that conforms to a rather standardized pattern. This response comprises the synthesis of inflammatory factors at hepatic and extra-hepatic sites.27,28 Pentraxins, in particular, are involved in the response against microbes. Recent data, however, indicate that they are recruited at sites of tissue damage and repair and influence female fertility.27 PTX3, which is generated in peripheral tissues under the control of inflammatory stimuli,27 edits the cross-presentation of epitopes expressed by apoptotic cells to T lymphocytes.35 Extensive cell death/tissue necrosis represents a challenge for the immune system because autoantigens are released in a context in which antigen presentation is favored. This is particularly important at the maternal/embryonic interface. Regulatory mechanisms exist at this level: apoptosis is a normal event during pregnancy,11,41 and potential substrates for cross-presentation are generated without enforcing a maternal immunization against the embryo. Dying cells possibly play a role in eliciting the inflammatory response that represents a normal feature of pregnancy. In this study we describe the constitutive generation of PTX3 in normal placentas, in which apoptosis allows the continuous renewal of the syncytial surface. Moreover, massive apoptosis takes place during labor, in parallel with the increased cell turnover and the alteration of the extracellular matrix,37 processes associated with the physiological involution of the placenta. PTX3 is therefore generated physiologically when apoptosis takes place during pregnancy. PTX3 selectively binds to late apoptotic and necrotic cells.34 It specifically concentrates at the phagocyte synapse between dying and dendritic cells where it actively restricts the activation of T cells specific for apoptotic cell–associated antigens, including cytoskeleton components, tumor-associated antigens, and viral glycoproteins.35 In the developing placenta, PTX3 possibly has a key role in quenching the cross-presentation of antigens of the embryo to maternal T lymphocytes, thus preventing alloimmunization.

Damaged areas are much more common in preeclamptic placentas then in placentas derived from normotensive women at comparable gestational ages.13 Accordingly, PTX3 levels rise in preeclamptic patients, whose tissues cope with a substantially higher load of placental debris.4 Variable, but intense, expression of PTX3, detected by immunohistochemistry, confirms these data. The constant negative immunostaining of endothelial cells in normal and preeclamptic placentas further indicates that different stimuli are involved compared with other conditions in which PTX3 has been detected in inflamed tissues, like systemic small-vessel vasculitis.19 Both maternal-fetal immune maladaption, with generation of antigenic stimuli and T helper 1 cell activation, and vascular events leading to placenta ischemia/reperfusion have been convincingly implicated in the pathogenesis of preeclampsia.11,13,42 Further studies are ongoing to verify whether PTX3 elevation actually reflects the action of relevant immunologic events in situ, possibly via activation of decidual and trophoblast, peculiarly extravillous, cells.


   Footnotes
 
This work was supported by the E.C. (APOCLEAR project) and by the Associazione Italiana per la Ricerca sul Cancro (AIRC).

Corresponding author: Patrizia Rovere-Querini MD, PhD, H. San Raffaele Scientific Institute, DIBIT 3A1, via Olgettina 58, 20132 Milano, Italy; e-mail: rovere.patrizia{at}hsr.it.

doi:10.1097/01.AOG.0000224607.46622.bc


   REFERENCES
TOP
ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
1. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science 2005;308:1592–4.[Abstract/Free Full Text]

2. Huppertz B, Frank HG, Kingdom JC, Reister F, Kaufmann P. Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. Histochem Cell Biol 1998;110:495–508.[Medline]

3. Blois S, Tometten M, Kandil J, Hagen E, Klapp BF, Margni RA, et al. Intercellular adhesion molecule-1/LFA-1 cross talk is a proximate mediator capable of disrupting immune integration and tolerance mechanism at the feto-maternal interface in murine pregnancies. J Immunol 2005;174:1820–9.[Abstract/Free Full Text]

4. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365:785–99.[Medline]

5. Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol 2005;105:402–10.[Abstract/Free Full Text]

6. Allaire AD, Ballenger KA, Wells SR, McMahon MJ, Lessey BA. Placental apoptosis in preeclampsia. Obstet Gynecol 2000;96:271–6.[Abstract/Free Full Text]

7. Abrahams VM, Kim YM, Straszewski SL, Romero R, Mor G. Macrophages and apoptotic cell clearance during pregnancy. Am J Reprod Immunol 2004;51:275–82.[Medline]

8. Hsu CD, Harirah H, Basherra H, Mor G. Serum soluble Fas levels in preeclampsia. Obstet Gynecol 2001;97:530–2.[Abstract/Free Full Text]

9. Ishihara N, Matsuo H, Murakoshi H, Laoag-Fernandez JB, Samoto T, Maruo T. Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am J Obstet Gynecol 2002;186:158–66.[Medline]

10. Huppertz B, Kingdom J, Caniggia I, Desoye G, Black S, Korr H, et al. Hypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation. Placenta 2003;24:181–90.[Medline]

11. Huppertz B, Kingdom JC. Apoptosis in the trophoblast–role of apoptosis in placental morphogenesis. J Soc Gynecol Investig 2004;11:353–62.[Medline]

12. Lee H, Park H, Kim YJ, Kim HJ, Ahn YM, Park B, et al. Expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in human preeclamptic placenta: possible implications in the process of trophoblast apoptosis. Placenta 2005;26:226–33.[Medline]

13. Moldenhauer JS, Stanek J, Warshak C, Khoury J, Sibai B. The frequency and severity of placental findings in women with preeclampsia are gestational age dependent. Am J Obstet Gynecol 2003;189:1173–7.[Medline]

14. Kwaan HC, Wang J, Boggio L, Weiss I, Grobman WA. The thrombogenic effect of an inflammatory cytokine on trophoblasts from women with preeclampsia. Am J Obstet Gynecol 2004;191:2142–7.[Medline]

15. Zimmermann VS, Bondanza A, Monno A, Rovere-Querini P, Corti A, Manfredi AA. TNF-alpha coupled to membrane of apoptotic cells favors the cross-priming to melanoma antigens. J Immunol 2004;172:2643–50.[Abstract/Free Full Text]

16. Lee GW, Lee TH, Vilcek J. TSG-14, a tumor necrosis factor- and IL-1-inducible protein, is a novel member of the pentaxin family of acute phase proteins. J Immunol 1993;150:1804–12.[Abstract]

17. Breviario F, d'Aniello EM, Golay, J, Peri G, Bottazzi B, Bairoch A, et al. Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. J Biol Chem 1992;267:22190–7.[Abstract/Free Full Text]

18. Peri G, Introna M, Corradi D, Iacuitti G, Signorini S, Avanzini F, et al. PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans. Circulation 2000;102:636–41.[Abstract/Free Full Text]

19. Fazzini F, Peri G, Doni A, Dell'Antonio G, Dal Cin E, Bozzolo E, et al. PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. Arthritis Rheum 2001;44:2841–50.[Medline]

20. Luchetti MM, Piccinini G, Mantovani A, Peri G, Matteucci C, Pomponio G, et al. Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA). Clin Exp Immunol 2000;119:196–202.[Medline]

21. Muller B, Peri G, Doni A, Torri V, Landmann R, Bottazzi B, et al. Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients. Crit Care Med 2001;29:1404–7.[Medline]

22. Latini R, Maggioni AP, Peri G, Gonzini L, Lucci D, Mocarelli P, et al. Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction PTX3. Circulation 2004;110:2349–54.[Abstract/Free Full Text]

23. al-Ramadi BK, Ellis M, Pasqualini F, Mantovani A. Selective induction of pentraxin 3, a soluble innate immune pattern recognition receptor, in infectious episodes in patients with haematological malignancy. Clin Immunol 2004;112:221–4.[Medline]

24. Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R, et al. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 2002;420:182–6.[Medline]

25. Varani S, Elvin JA, Yan C, DeMayo J, DeMayo FJ, Horton HF, et al. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol 2002;16:1154–67.[Abstract/Free Full Text]

26. Salustri A, Garlanda C, Hirsch E, De Acetis M, Maccagno A, Bottazzi B, et al. PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development 2004;131:1577–86.[Abstract/Free Full Text]

27. Garlanda C, Bottazzi B, Bastone A, Mantovani A. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition and female fertility. Annu Rev Immunol 2005;23:337–66.[Medline]

28. Bottazzi B, Garlanda C, Salvatori G, Jeannin P, Manfredi A, Mantovani A. Pentraxins as a key component of innate immunity. Curr Opin Immunol 2006;18:10–5.[Medline]

29. Alles VV, Bottazzi B, Peri G, Golay J, Introna M, Mantovani A. Inducible expression of PTX3, a new member of the pentraxin family, in human mononuclear phagocytes. Blood 1994;84:3483–93.[Abstract/Free Full Text]

30. Introna M, Alles VV, Castellano M, Picardi G, De Gioia, L, Bottazzi B, et al. Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites. Blood 1996;87:1862–72.[Abstract/Free Full Text]

31. Doni A, Peri G, Chieppa M, Allavena P, Pasqualini F, Vago L, et al. Production of the soluble pattern recognition receptor PTX3 by myeloid, but not plasmacytoid, dendritic cells. Eur J Immunol 2003;33:2886–93.[Medline]

32. Abderrahim-Ferkoune A, Bezy O, Astri-Roques S, Elabd C, Ailhaud G, Amri EZ, et al. Transdifferentiation of preadipose cells into smooth muscle-like cells: role of aortic carboxypeptidase-like protein. Exp Cell Res 2004;293:219–28.[Medline]

33. Klouche M, Peri G, Knabbe C, Eckstein HH, Schmid FX, Schmitz G, Mantovani A. Modified atherogenic lipoproteins induce expression of pentraxin-3 by human vascular smooth muscle cells. Atherosclerosis 2004;175:221–8.[Medline]

34. Rovere P, Peri G, Fazzini F, Bottazzi B, Doni A, Bondanza A, et al. The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells. Blood 2000;96:4300–6.[Abstract/Free Full Text]

35. Baruah P, Propato A, Dumitriu IE, Rovere-Querini P, Russo V, Fontana R, et al. 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. Blood 2006;107:151–8.[Abstract/Free Full Text]

36. Vouret-Craviari V, Cenzuales S, Poli G, Mantovani A. Expression of monocyte chemotactic protein-3 in human monocytes exposed to the mycobacterial cell wall component lipoarabinomannan. Cytokine 1997;9:992–8.[Medline]

37. Menon R, Fortunato SJ. The role of matrix degrading enzymes and apoptosis in rupture of membranes. J Soc Gynecol Investig 2004;11:427–37.[Medline]

38. Bianchi ME, Manfredi A. Chromatin and cell death. Biochim Biophys Acta 2004;1677:181–6.[Medline]

39. Gaipl US, Franz S, Voll RE, Sheriff A, Kalden JR, Herrmann M. Defects in the disposal of dying cells lead to autoimmunity. Curr Rheumatol Rep 2004;6:401–7.[Medline]

40. Rovere-Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, et al. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 2004;5:825–30.[Medline]

41. Bischoff FZ, Lewis DE, Simpson JL. Cell-free fetal DNA in maternal blood: kinetics, source, and structure. Hum Reprod Update 2005;11:59–67.[Abstract/Free Full Text]

42. Shu F, Sugimura M, Kanayama N, Kobayashi H, Kobayashi T, Terao T. Immunohistochemical study of annexin V expression in placentae of preeclampsia. Gynecol Obstet Invest 2000;49:17–23.[Medline]




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