The atypical chemokine receptor-2 does not alter corneal graft survival but regulates early stage of corneal graft induced lymphangiogenesis

Tian Yu, John V. Forrester, Gerard J. Graham, Lucia Kuffova

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Abstract

Purpose: To re-evaluate the role of the atypical chemokine receptor-2 (ACKR2) in corneal graft rejection and investigate the effect of ACKR2 on inflammation associated-lymphangiogenesis using murine orthotopic corneal transplantation.

Methods: Corneal grafts were performed and evaluated in the settings of syngeneic, allogeneic and single antigen (HY-antigen) disparity pairings. Corneal vessels were quantified in whole mounts from WT, ACKR2-/-, and F4/80-/-ACKR2-/- mice that received syngeneic or allogeneic grafts using anti-CD31 and anti-Lyve-1 antibodies.

Results: Syngeneic corneal grafts in WT and ACKR2-/- mice were 100% accepted. Fully histo-incompatible allogeneic grafts were rapidly rejected (100%) with similar tempo in both WT and ACKR2-/- hosts. Around 50% of single-antigen (HY) disparity grafts rejected at a slow but similar tempo (60 days) in WT and ACKR2-/- mice. Prior to grafting, F4/80-/-ACKR2-/- mice had lower baseline levels of limbal blood and lymphatic vessels compared to ACKR2-/- mice. Syngeneic grafts, but not allogeneic grafts, in ACKR2-/- and F4/80-/-ACKR2-/- mice induced higher levels of lymphatic sprouting and infiltration of Lyve-1+ cells during the early (3d) post graft (pg) stage but lymphatic density was similar to WT grafted mice by 7d pg.

Conclusions: Our results indicate that the chemokine scavenger receptor, ACKR2, has no role to play in the survival of allogeneic grafts. A minor role in regulation of lymphangiogenesis in the early stage of wound healing in syngeneic grafts is suggested but this effect is probably masked by the more pronounced lymphangiogenic inflammatory response in allogeneic grafts. No additional effect was observed with the deletion of the resident macrophage gene, F4/80.
Original languageEnglish
Pages (from-to)1875-1882
Number of pages8
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume256
Issue number10
Early online date27 Jul 2018
DOIs
Publication statusPublished - Oct 2018

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Lymphangiogenesis
Chemokine Receptors
Graft Survival
Transplants
H-Y Antigen
Scavenger Receptors
Lymphatic Vessels
Corneal Transplantation
Graft Rejection
Wound Healing

Keywords

  • ACKR2
  • corneal transplantation
  • lymphangiogenesis
  • angiogenesis
  • graft rejection
  • chemokines

Cite this

@article{536cf767378f41f696b16480dd690642,
title = "The atypical chemokine receptor-2 does not alter corneal graft survival but regulates early stage of corneal graft induced lymphangiogenesis",
abstract = "Purpose: To re-evaluate the role of the atypical chemokine receptor-2 (ACKR2) in corneal graft rejection and investigate the effect of ACKR2 on inflammation associated-lymphangiogenesis using murine orthotopic corneal transplantation.Methods: Corneal grafts were performed and evaluated in the settings of syngeneic, allogeneic and single antigen (HY-antigen) disparity pairings. Corneal vessels were quantified in whole mounts from WT, ACKR2-/-, and F4/80-/-ACKR2-/- mice that received syngeneic or allogeneic grafts using anti-CD31 and anti-Lyve-1 antibodies.Results: Syngeneic corneal grafts in WT and ACKR2-/- mice were 100{\%} accepted. Fully histo-incompatible allogeneic grafts were rapidly rejected (100{\%}) with similar tempo in both WT and ACKR2-/- hosts. Around 50{\%} of single-antigen (HY) disparity grafts rejected at a slow but similar tempo (60 days) in WT and ACKR2-/- mice. Prior to grafting, F4/80-/-ACKR2-/- mice had lower baseline levels of limbal blood and lymphatic vessels compared to ACKR2-/- mice. Syngeneic grafts, but not allogeneic grafts, in ACKR2-/- and F4/80-/-ACKR2-/- mice induced higher levels of lymphatic sprouting and infiltration of Lyve-1+ cells during the early (3d) post graft (pg) stage but lymphatic density was similar to WT grafted mice by 7d pg.Conclusions: Our results indicate that the chemokine scavenger receptor, ACKR2, has no role to play in the survival of allogeneic grafts. A minor role in regulation of lymphangiogenesis in the early stage of wound healing in syngeneic grafts is suggested but this effect is probably masked by the more pronounced lymphangiogenic inflammatory response in allogeneic grafts. No additional effect was observed with the deletion of the resident macrophage gene, F4/80.",
keywords = "ACKR2, corneal transplantation, lymphangiogenesis, angiogenesis, graft rejection, chemokines",
author = "Tian Yu and Forrester, {John V.} and Graham, {Gerard J.} and Lucia Kuffova",
note = "Open Access via Springer Compact Agreement Funding: Saving Sight in Grampian provided financial support in the forming of Saving Sight in Grampian funding. The sponsor had no role in the design or conduct of this research.",
year = "2018",
month = "10",
doi = "10.1007/s00417-018-4070-1",
language = "English",
volume = "256",
pages = "1875--1882",
journal = "Graefe's Archive for Clinical and Experimental Ophthalmology",
issn = "0721-832X",
publisher = "Springer Verlag",
number = "10",

}

TY - JOUR

T1 - The atypical chemokine receptor-2 does not alter corneal graft survival but regulates early stage of corneal graft induced lymphangiogenesis

AU - Yu, Tian

AU - Forrester, John V.

AU - Graham, Gerard J.

AU - Kuffova, Lucia

N1 - Open Access via Springer Compact Agreement Funding: Saving Sight in Grampian provided financial support in the forming of Saving Sight in Grampian funding. The sponsor had no role in the design or conduct of this research.

PY - 2018/10

Y1 - 2018/10

N2 - Purpose: To re-evaluate the role of the atypical chemokine receptor-2 (ACKR2) in corneal graft rejection and investigate the effect of ACKR2 on inflammation associated-lymphangiogenesis using murine orthotopic corneal transplantation.Methods: Corneal grafts were performed and evaluated in the settings of syngeneic, allogeneic and single antigen (HY-antigen) disparity pairings. Corneal vessels were quantified in whole mounts from WT, ACKR2-/-, and F4/80-/-ACKR2-/- mice that received syngeneic or allogeneic grafts using anti-CD31 and anti-Lyve-1 antibodies.Results: Syngeneic corneal grafts in WT and ACKR2-/- mice were 100% accepted. Fully histo-incompatible allogeneic grafts were rapidly rejected (100%) with similar tempo in both WT and ACKR2-/- hosts. Around 50% of single-antigen (HY) disparity grafts rejected at a slow but similar tempo (60 days) in WT and ACKR2-/- mice. Prior to grafting, F4/80-/-ACKR2-/- mice had lower baseline levels of limbal blood and lymphatic vessels compared to ACKR2-/- mice. Syngeneic grafts, but not allogeneic grafts, in ACKR2-/- and F4/80-/-ACKR2-/- mice induced higher levels of lymphatic sprouting and infiltration of Lyve-1+ cells during the early (3d) post graft (pg) stage but lymphatic density was similar to WT grafted mice by 7d pg.Conclusions: Our results indicate that the chemokine scavenger receptor, ACKR2, has no role to play in the survival of allogeneic grafts. A minor role in regulation of lymphangiogenesis in the early stage of wound healing in syngeneic grafts is suggested but this effect is probably masked by the more pronounced lymphangiogenic inflammatory response in allogeneic grafts. No additional effect was observed with the deletion of the resident macrophage gene, F4/80.

AB - Purpose: To re-evaluate the role of the atypical chemokine receptor-2 (ACKR2) in corneal graft rejection and investigate the effect of ACKR2 on inflammation associated-lymphangiogenesis using murine orthotopic corneal transplantation.Methods: Corneal grafts were performed and evaluated in the settings of syngeneic, allogeneic and single antigen (HY-antigen) disparity pairings. Corneal vessels were quantified in whole mounts from WT, ACKR2-/-, and F4/80-/-ACKR2-/- mice that received syngeneic or allogeneic grafts using anti-CD31 and anti-Lyve-1 antibodies.Results: Syngeneic corneal grafts in WT and ACKR2-/- mice were 100% accepted. Fully histo-incompatible allogeneic grafts were rapidly rejected (100%) with similar tempo in both WT and ACKR2-/- hosts. Around 50% of single-antigen (HY) disparity grafts rejected at a slow but similar tempo (60 days) in WT and ACKR2-/- mice. Prior to grafting, F4/80-/-ACKR2-/- mice had lower baseline levels of limbal blood and lymphatic vessels compared to ACKR2-/- mice. Syngeneic grafts, but not allogeneic grafts, in ACKR2-/- and F4/80-/-ACKR2-/- mice induced higher levels of lymphatic sprouting and infiltration of Lyve-1+ cells during the early (3d) post graft (pg) stage but lymphatic density was similar to WT grafted mice by 7d pg.Conclusions: Our results indicate that the chemokine scavenger receptor, ACKR2, has no role to play in the survival of allogeneic grafts. A minor role in regulation of lymphangiogenesis in the early stage of wound healing in syngeneic grafts is suggested but this effect is probably masked by the more pronounced lymphangiogenic inflammatory response in allogeneic grafts. No additional effect was observed with the deletion of the resident macrophage gene, F4/80.

KW - ACKR2

KW - corneal transplantation

KW - lymphangiogenesis

KW - angiogenesis

KW - graft rejection

KW - chemokines

U2 - 10.1007/s00417-018-4070-1

DO - 10.1007/s00417-018-4070-1

M3 - Article

VL - 256

SP - 1875

EP - 1882

JO - Graefe's Archive for Clinical and Experimental Ophthalmology

JF - Graefe's Archive for Clinical and Experimental Ophthalmology

SN - 0721-832X

IS - 10

ER -