ArticlePloS one2017
Increased migration of antigen presenting cells to newly-formed lymphatic vessels in transplanted kidneys by glycol-split heparin.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Organ-specific features of human kidney lymphatics are disrupted in chronic transplant rejection.The Journal of clinical investigation · 2025Article
- Modelling innate and adaptive immune responses in whole blood: A modifiedJournal of biological methods · 2025Article
- The immune regulatory role of lymphangiogenesis in kidney disease.Journal of translational medicine · 2024Review
- Prevention of Triglyceridemia by (Non-)Anticoagulant Heparin(oids) Does Not Preclude Transplant Vasculopathy and Glomerulosclerosis.Frontiers in cell and developmental biology · 2022Article
- Analyzing Lymphatic Vessel Patterning in Adult Tissue.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The lymphatics in kidney health and disease.Nature reviews. Nephrology · 2021Review
- Auditory brainstem responses in aging dark agouti rats.Bioscience reports · 2021Article
- Lymphatic Reconstruction in Kidney Allograft Aggravates Chronic Rejection by Promoting Alloantigen Presentation.Frontiers in immunology · 2021Article
- Beyond a Passive Conduit: Implications of Lymphatic Biology for Kidney Diseases.Journal of the American Society of Nephrology : JASN · 2020Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChronic renal transplant dysfunction is characterized by loss of renal function and tissue remodeling, including chronic inflammation and lymph vessel formation. Proteoglycans are known for their chemokine presenting capacity. We hypothesize that interruption of the lymphatic chemokine-proteoglycan interaction interferes with the lymphatic outflow of leukocytes from the renal graft and might decrease the anti-graft allo-immune response.
methodsIn a rat renal chronic transplant dysfunction model (female Dark-Agouti to male Wistar Furth), chemokines were profiled by qRT-PCR in microdissected tubulo-interstitial tissue. Disruption of lymphatic chemokine-proteoglycan interaction was studied by (non-anticoagulant) heparin-derived polysaccharides in vitro and in renal allografts. The renal allograft function was assessed by rise in plasma creatinine and urea.
resultsWithin newly-formed lymph vessels of transplanted kidneys, numerous CD45+ leukocytes were found, mainly MHCII+, ED-1-, IDO-, HIS14-, CD103- antigen presenting cells, most likely representing a subset of dendritic cells. Treatment of transplanted rats with regular heparin and two different (non-)anticoagulant heparin derivatives revealed worsening of kidney function only in the glycol-split heparin treated group despite a two-fold reduction of tubulo-interstitial leukocytes (p<0.02). Quantitative digital image analysis however revealed increased numbers of intra-lymphatic antigen-presenting cells only in the glycol-split heparin group (p<0.01). The number of intra-lymphatic leukocytes significantly correlates with plasma creatinine and urea, and inversely with creatinine clearance.
conclusionsTreatment of transplanted rats with glycol-split heparin significantly increases the number of intra-lymphatic antigen presenting cells, by increased renal diffusion of lymphatic chemokines, thereby increasing the activation and recruitment of antigen presenting cells towards the lymph vessel. This effect is unwanted in the transplantation setting, but might be advantageous in e.g., dendritic cell vaccination.
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