Erythroblast differentiation at spleen in Q137E mutant ribosomal protein S19 gene knock-in C57BL/6J mice

Immunobiology. 2018 Jan;223(1):118-124. doi: 10.1016/j.imbio.2017.10.003. Epub 2017 Oct 5.

Abstract

We recently found that erythroblast-like cells derived from human leukaemia K562 cells express C5a receptor (C5aR) and produce its antagonistic and agonistic ligand ribosomal protein S19 (RP S19) polymer, which is cross-linked between K122 and Q137 by tissue transglutaminases. RP S19 polymer binds to the reciprocal C5aRs on erythroblast-like cells and macrophage-like cells derived from human monocytic THP-1 cells and promotes differentiation into reticulocyte-like cells through enucleation in vitro. To examine the roles of RP S19 polymer in mouse erythropoiesis, we prepared Q137E mutant RP S19 gene knock-in C57BL/6J mice. In contrast to wild-type mice, erythroblast numbers at the preliminary stage (CD71high/TER119low) in spleen based on transferrin receptor (CD71) and glycophorin A (TER119) values and erythrocyte numbers in orbital artery bloods were not largely changed in knock-in mice. Conversely, erythroblast numbers at the early stage (CD71high/TER119high) were significantly decreased in spleen by knock-in mice. The reduction of early erythroblast numbers in spleen was enhanced by the phenylhydrazine-induced pernicious anemia model knock-in mice and was rescued by a functional analogue of RP S19 dimer S-tagged C5a/RP S19. These data indicated that RP S19 polymer plays the roles in the early erythroblast differentiation of C57BL/6J mouse spleen.

Keywords: C5a receptor; Erythroblasts; Glycophorin A; Ribosomal protein S19; Transferrin receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Pernicious / chemically induced
  • Anemia, Pernicious / immunology*
  • Animals
  • Antigens, CD / metabolism
  • Cell Differentiation
  • Disease Models, Animal
  • Erythroblasts / physiology*
  • Erythropoiesis / genetics
  • Gene Knock-In Techniques
  • Humans
  • K562 Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / physiology*
  • Mutation / genetics*
  • Phenylhydrazines / toxicity
  • Receptor, Anaphylatoxin C5a / metabolism
  • Receptors, Transferrin / metabolism
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism
  • Spleen / pathology
  • THP-1 Cells
  • Transglutaminases / metabolism

Substances

  • Antigens, CD
  • C5AR1 protein, human
  • CD71 antigen
  • Phenylhydrazines
  • Receptor, Anaphylatoxin C5a
  • Receptors, Transferrin
  • Ribosomal Proteins
  • ribosomal protein S19
  • phenylhydrazine
  • Transglutaminases