Heart allograft lymphatic system changes and quilty lesion

Beletskaya, L. V.; Kupriyanova, А. G.; Baranova, F. S.; Shumakov, Valerij I.

doi:10.1016/j.healun.2005.03.007

Cited by 5 publications

(3 citation statements)

References 2 publications

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“…13 In addition, lymphatic vessels have been detected in association with subendocardial lymphonodular aggregates (Quilty lesions), 25,26 and alteration of lymphatic EC markers has been observed during the first year after heart transplantation. 27 Here, we found that chronic rejection increased lymphangiogenesis in rat cardiac allografts.…”

Section: Discussionmentioning

confidence: 99%

Targeting Lymphatic Vessel Activation and CCL21 Production by Vascular Endothelial Growth Factor Receptor-3 Inhibition Has Novel Immunomodulatory and Antiarteriosclerotic Effects in Cardiac Allografts

Nykänen

Sandelin²,

Krebs³

et al. 2010

Circulation

137

129

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Background— Lymphatic network and chemokine-mediated signals are essential for leukocyte traffic during the proximal steps of alloimmune response. We aimed to determine the role of lymphatic vessels and their principal growth signaling pathway, vascular endothelial growth factor (VEGF)-C/D/VEGFR-3, during acute and chronic rejection in cardiac allografts. Methods and Results— Analysis of heterotopically transplanted rat cardiac allografts showed that chronic rejection increased VEGF-C + inflammatory cell and hyaluronan receptor-1 (LYVE-1) + lymphatic vessel density. Allograft lymphatic vessels were VEGFR-3 + , contained antigen-presenting cells, and produced dendritic cell chemokine CCL21. Experiments with VEGFR-3/LacZ mice or mice with green fluorescent protein–positive bone marrow cells as cardiac allograft recipients showed that allograft lymphatic vessels originated almost exclusively from donor cells. Intraportal adenoviral VEGFR-3-Ig (Ad.VEGFR-3-Ig/VEGF-C/D-Trap) perfusion was used to inhibit VEGF-C/D/VEGFR-3 signaling. Recipient treatment with Ad.VEGFR-3-Ig prolonged rat cardiac allograft survival. Ad.VEGFR-3-Ig did not affect allograft lymphangiogenesis but was linked to reduced CCL21 production and CD8 + effector cell entry in the allograft. Concomitantly, Ad.VEGFR-3-Ig reduced OX62 + dendritic cell recruitment and increased transcription factor Foxp3 expression in the spleen. In separate experiments, treatment with a neutralizing monoclonal VEGFR-3 antibody reduced arteriosclerosis, the number of activated lymphatic vessels expressing VEGFR-3 and CCL21, and graft-infiltrating CD4 + T cells in chronically rejecting mouse cardiac allografts. Conclusions— These results show that VEGFR-3 participates in immune cell traffic from peripheral tissues to secondary lymphoid organs by regulating allograft lymphatic vessel CCL21 production and suggest VEGFR-3 inhibition as a novel lymphatic vessel–targeted immunomodulatory therapy for cardiac allograft rejection and arteriosclerosis.

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Section: Discussionmentioning

confidence: 99%

Targeting Lymphatic Vessel Activation and CCL21 Production by Vascular Endothelial Growth Factor Receptor-3 Inhibition Has Novel Immunomodulatory and Antiarteriosclerotic Effects in Cardiac Allografts

Nykänen

Sandelin²,

Krebs³

et al. 2010

Circulation

137

129

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“…The presence of fibrin in the interstitial space is a reliable marker of rejection crisis, but it characteristic of both humoral and cellular rejection. Therefore, detection of C4d complement component resistant to catalysis was an important finding; it was characterized as a humoral rejection marker [6,7,11]. Some authors [9] noted that signs of humoral rejection of the heart allotransplant are most often observed during the first 6-8 weeks after the organ transplantation.…”

Section: Resultsmentioning

confidence: 99%

Rheumatoid course of humoral (vascular) rejection after heart allotransplantation

et al. 2006

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“…Beletskaya с соавт. [14] связывают возникновение эффекта Quilty с повреждением стенки лимфатических сосудов и выходом лимфоцитов в эндокард трансплантированного сердца. Однако в литературе более всего обсуждается взаимосвязь между эффектом Quilty и ингибиторами кальциневрина, острым или хроническим отторжением.…”

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Etiology, Pathogenesis and Morphology of the Quilty Effect

Alexeeva¹,

Iljinsky²

2015

Russian Journal of Transplantology and Artificial Organs

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ФГБУ «ФНЦ трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, г. Москва 2 Кафедра трансплантологии и искусственных органов I МГМУ имени И.М. Сеченова, г. Москва Несмотря на то что изучение эндокардиальных инфильтратов (Quilty effect) в трансплантированном сердце продолжается уже более 30 лет, этиология, морфология и клиническое значение этого феномена остаются до конца не выясненными. В статье приведены данные доступной литературы о возможных причинах и механизмах развития эффекта Quilty, а также о его влиянии на функцию трансплантированного сердца.

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Heart allograft lymphatic system changes and quilty lesion

Cited by 5 publications

References 2 publications

Targeting Lymphatic Vessel Activation and CCL21 Production by Vascular Endothelial Growth Factor Receptor-3 Inhibition Has Novel Immunomodulatory and Antiarteriosclerotic Effects in Cardiac Allografts

Targeting Lymphatic Vessel Activation and CCL21 Production by Vascular Endothelial Growth Factor Receptor-3 Inhibition Has Novel Immunomodulatory and Antiarteriosclerotic Effects in Cardiac Allografts

Rheumatoid course of humoral (vascular) rejection after heart allotransplantation

Etiology, Pathogenesis and Morphology of the Quilty Effect

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