Recipient Neutrophils Producing Myeloperoxidase Provoke Nk Cell and Monocyte/macrophage Activation During Acute Antibody-mediated Rejection of Kidney Allografts

D. Ueda, S. Miyairi, K. Keslar, W. M. Baldwin, R. L. Fairchild

Lerner Research Institute, Cleveland Clinic, Cleveland, OH

Meeting: 2021 American Transplant Congress

Abstract number: 555

Keywords: Natural killer cells, Rejection

Topic: Basic Science » Innate Immunity; Chemokines, Cytokines, Complement

Session Information

Session Name: Innate Immunity; Chemokines, Cytokines, Complement

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: Dysregulated donor-specific antibody (DSA) responses are induced in B6.CCR5^-/- mice transplanted with complete MHC mismatched A/J kidney allografts and mediate acute graft rejection. Acute antibody-mediated rejection (AMR) also requires NK cell and myeloid cell activation to express effector functions within the graft.

*Methods: This study used recipients deficient in myeloperoxidase (MPO) to test the influence of recipient myeloid cells on NK cell activation during acute AMR.

*Results: B6.CCR5^-/- recipients rejected A/J kidneys between days 18-25 vs. days 46-54 in B6.CCR5^-/-MPO^-/- recipients, despite equivalent DSA titers. On day 15, NK cell activation to proliferate and express CD107a was markedly decreased within allografts in B6.CCR5^-/-MPO^-/- recipients. RNA isolated from purified allograft infiltrating NK cells, monocytes and macrophages on day 15 post-transplant was interrogated by NanoString and indicated completely different transcript landscapes in all 3 leukocyte populations from B6.CCR5^-/-MPO^-/- vs. B6.CCR5^-/- recipients that correlated with development of acute vs. chronic allograft injury, respectively.

*Conclusions: Neutrophil depletion abrogated NK cell activation and decreased macrophage infiltration into the allografts but increased monocytes producing MPO. Overall, the results indicate that neutrophils regulate graft-infiltrating NK cell activation and monocytes/macrophage development promoting acute AMR of kidney allografts.

To cite this abstract in AMA style:

Ueda D, Miyairi S, Keslar K, Baldwin WM, Fairchild RL. Recipient Neutrophils Producing Myeloperoxidase Provoke Nk Cell and Monocyte/macrophage Activation During Acute Antibody-mediated Rejection of Kidney Allografts [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/recipient-neutrophils-producing-myeloperoxidase-provoke-nk-cell-and-monocyte-macrophage-activation-during-acute-antibody-mediated-rejection-of-kidney-allografts/. Accessed November 24, 2024.

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