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Author Notes:

Correspondence: Krystalyn E. Hudson krystalh@bloodworksnw.org

KH, Kd, LK, AR, MS, and JZ each performed experiments and analyzed data contained in this work.

KH and JZ authored the manuscript and Kd, LK, AR, and MS provided revisions.

All the authors read and approved of the manuscript.

The authors would like to thank Dr. Steven Spitalnik for his intellectual input and encouragement regarding these studies.

All procedures were performed according to approved BloodworksNW Institutional Animal Care and Use Committee (IACUC) protocols.

KH, Kd, LK, AR, and MS have no conflicts of interest to declare.

JZ serves on the Scientific Advisory Board for Rubius Therapeutics and consults or Surface Oncology and Sinopia Biosciences.

Subjects:

Research Funding:

This work was supported, in part, by the National Blood Foundation and discretionary funding from BloodworksNW.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • red blood cell clearance
  • complement C3
  • red blood cell lifespan
  • antibodies
  • senescent antigen
  • naturally occurring antibodies
  • OCCURRING ANTI-BAND-3 ANTIBODIES
  • IN-VIVO
  • ERYTHROCYTE PHAGOCYTOSIS
  • HUMAN-COMPLEMENT
  • 3RD COMPONENT
  • CLEARANCE
  • MICE
  • ERYTHROPHAGOCYTOSIS
  • PHOSPHATIDYLSERINE
  • MACROPHAGES

Antibodies to Senescent Antigen and C3 Are Not Required for Normal Red Blood Cell Lifespan in a Murine Model

Tools:

Journal Title:

Frontiers in Immunology

Volume:

Volume 8, Number OCT

Publisher:

, Pages 1425-1425

Type of Work:

Article | Final Publisher PDF

Abstract:

Red blood cells (RBCs) have a well-defined lifespan, indicating a mechanism by which senescent cells of a certain age are removed from circulation. However, the specifics by which senescent cells are recognized and removed are poorly understood. There are multiple competing hypotheses for this process, perhaps the most commonly cited is that senescent RBCs expose neoantigens [or senescent antigen(s)] that are then recognized by naturally occurring antibodies, which opsonize the senescent cells and result in clearance from circulation. While there are a large volume of published data to indicate that older RBCs accumulate increased levels of antibody on their surface, to the best of our knowledge, the causal role of such antibodies in clearance has not been rigorously assessed. In the current report, we demonstrate that RBC lifespan and clearance patterns are not altered in mice deficient in antibodies, in C3 protein, or missing both. These data demonstrate that neither antibody nor C3 is required for clearance of senescent RBCs, and questions if they are even involved, in a murine model of RBC lifespan.

Copyright information:

© 2017 Hudson, de Wolski, Kapp, Richards, Schniederjan and Zimring.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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