PMID- 33724240
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20231002
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 105
IP  - 11
DP  - 2021 Nov 1
TI  - Cellular and Molecular Crosstalk of Graft Endothelial Cells During AMR: Effector 
      Functions and Mechanisms.
PG  - e156-e167
LID - 10.1097/TP.0000000000003741 [doi]
AB  - Graft endothelial cell (EC) injury is central to the pathogenesis of 
      antibody-mediated rejection (AMR). The ability of donor-specific antibodies (DSA) 
      to bind C1q and activate the classical complement pathway is an efficient 
      predictor of graft rejection highlighting complement-dependent cytotoxicity as a 
      key process operating during AMR. In the past 5 y, clinical studies further 
      established the cellular and molecular signatures of AMR revealing the key 
      contribution of other, IgG-dependent and -independent, effector mechanisms 
      mediated by infiltrating NK cells and macrophages. Beyond binding to 
      alloantigens, DSA IgG can activate NK cells and mediate antibody-dependent cell 
      cytotoxicity through interacting with Fcgamma receptors (FcgammaRs) such as FcgammaRIIIa 
      (CD16a). FcRn, a nonconventional FcgammaR that allows IgG recycling, is highly 
      expressed on ECs and may contribute to the long-term persistence of DSA in blood. 
      Activation of NK cells and macrophages results in the production of 
      proinflammatory cytokines such as TNF and IFNgamma that induce transient and 
      reversible changes in the EC phenotype and functions promoting coagulation, 
      inflammation, vascular permeability, leukocyte trafficking. MHC class I mismatch 
      between transplant donor and recipient can create a situation of "missing self" 
      allowing NK cells to kill graft ECs. Depending on the microenvironment, cellular 
      proximity with ECs may participate in macrophage polarization toward an M1 
      proinflammatory or an M2 phenotype favoring inflammation or vascular repair. 
      Monocytes/macrophages participate in the loss of endothelial specificity in the 
      process of endothelial-to-mesenchymal transition involved in renal and cardiac 
      fibrosis and AMR and may differentiate into ECs enabling vessel and graft 
      (re)-endothelialization.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Charreau, Beatrice
AU  - Charreau B
AD  - CHU Nantes, Universite de Nantes, Inserm, Centre de Recherche en Transplantation 
      et en Immunologie, UMR 1064, ITUN, Nantes, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (HLA Antigens)
RN  - 0 (Isoantibodies)
SB  - IM
CIN - Transplantation. 2021 Nov 1;105(11):e154-e155. PMID: 33724241
MH  - Endothelial Cells
MH  - Graft Rejection
MH  - HLA Antigens
MH  - *Isoantibodies
MH  - *Kidney Transplantation/adverse effects
COIS- The author declares no conflicts of interest.
EDAT- 2021/03/17 06:00
MHDA- 2022/04/01 06:00
CRDT- 2021/03/16 12:30
PHST- 2021/03/17 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2021/03/16 12:30 [entrez]
AID - 00007890-202111000-00015 [pii]
AID - 10.1097/TP.0000000000003741 [doi]
PST - ppublish
SO  - Transplantation. 2021 Nov 1;105(11):e156-e167. doi: 10.1097/TP.0000000000003741.