Predictive Role of Pretransplant Serum CXCL10 for Cardiac Acute Rejection

Crescioli, Clara; Buonamano, Andrea; Scolletta, Sabino; Sottili, Mariangela; Francalanci, Michela; Giomarelli, Pierpaolo; Biagioli, Bonizella; Lisi, Gianfranco; Pradella, Fabio; Serio, Mario; Romagnani, Paola; Maccherini, Massimo

doi:10.1097/tp.0b013e3181919f5d

Cited by 38 publications

(32 citation statements)

References 38 publications

(33 reference statements)

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“…and CXCL11 (19). CXCL10, a factor determined to have the highest predictive value for early cardiac acute rejection (20), was initially reported to be induced by IFN-γ and secreted by various cell types, including monocytes, neutrophils, endothelial cells, keratinocytes and fibroblasts (21,22). After the first transplantation, CXCL10 was released into the circulation and recognized by CXCR3, which was expressed on the surface of Th1 cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

Deng

et al. 2017

Exp Ther Med

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Abstract. The interaction of chemokine (C-X-C motif) ligand 10 (CXCL10) with its receptor (CXCR3) is a critical process in recruiting donor reactive T cells to a graft and alloantigen-specific memory T (Tm) cells exert a principal function in promoting graft dysfunction during accelerated cardiac rejection. However, whether CXCL10 chemokine exerts any effects on acute accelerated rejection mediated by CD8 + Tm cells in a re-transplant model has remained elusive. The present study established a cardiac transplant model by advanced microsurgery technology and improved organ storage. A novel rat model of cardiac re-transplantation was established at 40 days following primary heart transplant. The experiment included two parts, and when models were established, the rats were divided into two groups: Primary cardiac transplant (HTx) and re-transplantation without treatment (HRTx). In part 1, recipients from part 2, including re-transplantation without treatment (HRTx+NS) and re-transplantation treated with anti-CXCL10 antibodies (500 µg every other day by intraperitoneal injection; HRTx+CXCL10 Abs group). The graft survival time was observed and graft infiltration by inflammatory cells was assessed via histology of cardiac graft sections; in addition, the gene expression and the serum concentration of CXCL10 in each group was assessed. Indexes such as rejection-associated cytokines were assayed by reverse-transcription quantitative PCR and ELISA kits, and flow cytometry of splenocytes was used to detect Tm cells in the re-transplantation groups. The results demonstrated that level of CXCL10 was significantly increased and the graft mean survival time was shortened accompanied with aggravated lymphocyte cell infiltration in the HRTx group when compared that in the HTx group; in addition, the serum levels and mRNA expression of interleukin (IL)-2 and interferon (IFN)-γ were increased, while transforming growth factor (TGF)-β was decreased in the HRTx group. Furthermore, neutralization of CXCL10 prolonged the graft mean survival time and delayed accelerated rejection. Compared with that in the HRTx+NS group, serum levels and graft tissue mRNA expression of IFN-γ and IL-2 were decreased in the HRTx+CXCL10 Abs group, while TGF-β mRNA was significantly increased but the serum concentration was not significantly affected. In addition, there was no difference in IL-10 between the two groups, while delayed accelerated rejection paralleled with inflammatory cell infiltration decreased and the proliferation and differentiation of CD8 + Tm cells in secondary lymphoid organs were reduced in the HRTx+CXCL10 Abs group vs. those in the HRTx+NS group. The present study demonstrated that CXCL10 had a crucial role in cardiac transplantation and re-transplantation, and that treatment with CXCL10 antibodies delays accelerated acute rejection mediated by Tm cells in a rat model of cardiac re-transplantation. IntroductionA multidisciplinary program has been initiated to better establish transplantation for prolonging survival time of cardi...

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Section: Discussionmentioning

confidence: 99%

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

Deng

et al. 2017

Exp Ther Med

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“…The role of CXCL10 in human leishmaniasis is not clear, although CXCL10 is well-known for its involvement in recruiting monocytes, M⌽s, T cells, and NK cells (29) during human viral and bacterial infections (18,26) and organ transplantation (8). By using a murine model of L. amazonensis infection, our group has previously shown that exogenous CXCL10 promotes parasite killing in M⌽ cultures in vitro (40) and enhances the antigen-presenting function in infected DCs (41) and that local injection of CXCL10 significantly delays the onset of cutaneous lesions (40).…”

Section: Discussionmentioning

confidence: 99%

CXCL10 Production by Human Monocytes in Response to Leishmania braziliensis Infection

Vargas-Inchaustegui¹,

Hogg²,

Tulliano

et al. 2010

Infect Immun

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Leishmania (subgenus Viannia) braziliensis is the causative agent of mucocutaneous leishmaniasis (ML) in South America, and ML is characterized by excessive T-and B-cell responses to the parasite. We speculate that the unbalanced production of inflammatory mediators in response to L. braziliensis infection contributes to cell recruitment and disease severity. To test this hypothesis, we first examined the response of peripheral blood mononuclear cells (PBMCs) from healthy volunteers to L. braziliensis infection. We observed that while L. braziliensis infection induced the production of chemokine (C-X-C motif) ligand 10 (CXCL10) and interleukin-10 (IL-10) in human PBMCs and macrophages (M⌽s), enhanced expression of CXCL10 and its receptor, chemokine CXC receptor (CXCR3), was predominantly detected in CD14 ؉ monocytes. The chemoattractant factors secreted by L. braziliensis-infected cells were highly efficient in recruiting uninfected PBMCs (predominantly CD14؉ cells) through Transwell membranes. Serum samples from American tegumentary leishmaniasis (ATL) patients (especially the ML cases) had significantly higher levels of CXCL10, CCL4, and soluble tumor necrosis factor (TNF) receptor II (sTNFRII) than did those of control subjects. Our results suggest that, following L. braziliensis infection, the production of multiple inflammatory mediators by the host may contribute to disease severity by increasing cellular recruitment.

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“…There is compelling evidence that CXCR3 and its ligands (CXCL9, CXCL10 and CXCL4) are implicated in the pathogenesis of transplant rejection [34,36,[44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]106]. For example, an increase in the concentration of CXCR3 ligands and the infiltration of CXCR3+ T cells has been demonstrated in biopsies from rejected solid organ transplants, including lungs [44], kidneys [107], skin [54] and endomyocardial tissue [46].…”

Section: The Role Of Cxcr3 In Transplant Rejectionmentioning

confidence: 99%

“…However, the binding of platelet-derived CXCR3 ligands induces angiostasis [34,93]. Due to the pleiotropic nature of CXCR3, the involvement of this receptor has been described in inflammatory, autoimmune and angiogenesis-related disorders such as inflammatory arthritis [94][95][96][97], systemic sclerosis [97][98][99][100], type I diabetes [97,101,102], transplant rejection [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] and cancer [36,38,[103][104][105].…”

Section: Cxcr3 Functions and Its Ligandsmentioning

confidence: 99%

“…This chemokine receptor is mainly expressed on T helper (Th)1 cells [40][41][42][43] and is up-regulated in activated lymphocytes recruited to the site of inflammation [34,37]. The expression of CXCR3 and its ligands (CXCL9, CXCL10 and CXCL11) is increased during allograft rejection [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]. CXCR3 is also expressed by the placenta (villous cytotrophoblasts and syncytiotrophoblasts) [63,64], the fetal membranes, and the choriodecidua of women who deliver term or preterm [64,65].…”

Section: Introductionmentioning

confidence: 99%

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Chronic inflammatory lesions of the placenta are associated with an up-regulation of amniotic fluid CXCR3: A marker of allograft rejection

Maymon

Romero

Bhatti

et al. 2018

Journal of Perinatal Medicine

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Objective: The objective of this study is to determine whether the amniotic fluid (AF) concentration of soluble CXCR3 and its ligands CXCL9 and CXCL10 changes in patients whose placentas show evidence of chronic chorioamnionitis or other placental lesions consistent with maternal anti-fetal rejection. Methods: This retrospective case-control study included 425 women with (1) preterm delivery (n = 92); (2) term in labor (n = 68); and (3) term not in labor (n = 265). Amniotic fluid CXCR3, CXCL9 and CXCL10 concentrations were determined by ELISA. Results: (1) Amniotic fluid concentrations of CXCR3 and its ligands CXCL9 and CXCL10 are higher in patients with preterm labor and maternal anti-fetal rejection lesions than in those without these lesions [CXCR3: preterm labor and delivery with maternal anti-fetal rejection placental lesions (median, 17.24 ng/mL; IQR, 6.79-26.68) vs. preterm labor and delivery without these placental lesions (median 8.79 ng/mL; IQR, 4.98-14.7; P = 0.028)]; (2) patients with preterm labor and chronic chorioamnionitis had higher AF concentrations of CXCL9 and CXCL10, but not CXCR3, than those without this lesion [CXCR3: preterm labor with chronic chorioamnionitis (median, 17.02 ng/mL; IQR, 5.57-26.68) vs. preterm labor without chronic chorioamnionitis (median, 10.37 ng/mL; IQR 5.01-17.81; P = 0.283)]; (3) patients with preterm labor had a significantly higher AF concentration of CXCR3 than those in labor at term regardless of the presence or absence of placental lesions. Conclusion: Our findings support a role for maternal antifetal rejection in a subset of patients with preterm labor.

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Predictive Role of Pretransplant Serum CXCL10 for Cardiac Acute Rejection

Abstract: In HTx recipients, measurement of pretransplant CXCL10 serum levels could be a clinically useful tool for predicting cardiac acute rejection, especially in the early posttransplant period.

Cited by 38 publications

References 38 publications

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

CXCL10 Production by Human Monocytes in Response to Leishmania braziliensis Infection

Chronic inflammatory lesions of the placenta are associated with an up-regulation of amniotic fluid CXCR3: A marker of allograft rejection

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